NERVE & MUSCLE PHYSIOLOGY-SEQs

19.5.2010

Q.1 What is END-PLATE POTENTIAL? How is it produced? In which disease end-plate potential is of low voltage? (2+2+1 mark) Key: END PLATE POTENTIAL: It is a local potential of motor end plate, i-e., the thickened muscle membrane that is supplied by a motor-neuron, thus forming a component of neuro-muscular junction. When impulse is transmitted from motor nerve to the muscle, the impulse arriving in the end of the motor neuron increases the permeability of its endings to calcium ions. Calcium ions trigger exocytosis of acetylcholine containing vesicles acetylcholine diffuses to the muscle-type nicotinic acetylcholine receptors, which are concentrated at the tops of junctional folds of the membrane of motor end plate. Binding of acetylcholine to these receptors increased sodium & potassium conductance of the membrane influx of sodium depolarizing potential is produced called END PLATE POTENTIAL The current created by this local potential depolarizes the adjacent muscle membrane to its firing level. Purpose of EPP is to build the threshold potential (- 65 mV). If RMP is -90 mV, then threshold is -65 mV, we need 25 mV potential change. Purpose of EPP is to reach the threshold of action potential. So voltage of EPP is much more than required, because required is only 25 mV. It is called SAFETY FACTOR. This is followed by removal of acetylcholine from synaptic cleft by acetylcholinesterase, present in high concentration at NMJ. Action potentials are generated on either side of end plate conducted away from end plate in both directions along muscle fiber. An average human end plate contains about 15 to 40 million acetylcholine receptors. Each nerve impulse releases about 60 acetylcholine vesicles, and each vesicle contains about 10,000 molecules of neurotransmitter. This amount is enough to activate about 10 times the number of acetylcholine receptors needed to produce a full end plate potential. So a propagated response in the muscle is regularly produced, and this response hides / obscures the end plate potential. However, EPP can be seen if the tenfold safety factor is

overcome & the potential is reduced to a size that is insufficient to fire the adjacent muscle membrane. This can be achieved by administration of small doses of curare, a drug that competes with acetylcholine for binding to muscle-type nicotinic acetylcholine receptors. Response is then recorded only at end plate region & decreases exponentially away from it. Under these conditions, EPPs can be shown to undergo temporal summation. (comparison table between EPP and Action Potential has been removed as advised & points of EPP only from the table are mentioned below) EPP: Local potential recorded only at End plate region. It varies with strength of stimulus / amount of neurotransmitter released. It can show summation. In Myasthenia Gravis, Miniature End Plate Potentials (MEPP = 0.5 mV) are produced. A rare auto-immune disease. Voltage of EPP is very low (Miniature EPP) action potential is not followed. At rest normally, a few synaptic vesicles break to liberate Ach from synaptic vesicles small change in EPP (about 0.5 mV) called MEPP. Amplitude varies directly with [Ca++] and inversely with [Mg++]. Impulse fails to transmit through NMJ Severe muscle weakness & fatigue (Extra-ocular muscles ptosis, diplopia, difficulty in Swallowing, weakness of Respiratory and Facial muscles) Q.2 Draw strength duration curve. Define the units of excitability & give their clinical application? What is meant by Utilization Time? (2+1+1+1 marks) Key:

Key:

Units of excitability are Rheobase and Chronaxie. RHEOBASE: Voltage or strength of stimulus required just to excite the tissue, e.g., 1mV. (0.5 mark) CHRONAXIE: A time for which a stimulus double the rheobase, when applied, just excites the tissue, e.g., 2 mV. It is a unit of time. (0.5 mark) Damage to nerve fiber is determined by measuring Chronaxie. Most excitable fibers have minimum value of Chronaxie. (1 mark) The time for which Rheobase must be applied to excite the tissue is UTILIZATION TIME. (1 mark)

Q.3 What is Spike Potential? Why sodium ions cannot pass through potassium channels? Give the ionic basis of Absolute Refractory Period, After Depolarization and After Hyperpolarization. (1+1+1+1+1 mark) Key:

KEY: SPIKE POTENTIAL: Part of action potential between threshold value and beginning of after depolarization is called Spike potential. (1 mark) Sodium channels have highly negative charge on inside. Hydrated form of Sodium ions is larger. Size of Potassium channels is smaller, so Sodium cannot pass through Potassium channels. (1 mark) Absolute refractory period includes depolarization and first 1/3 of repolarization. Sodium inactivation gates are still closed and will not open till potential reaches resting value. (1 mark) During repolarization, Potassium becomes accumulated on outer side of membrane which slows down further efflux after 70% of repolarization leading to slow repolarization called After depolarization. (1 mark) When potential has reached the resting value, it does not stay there and becomes more negative and called After hyperpolarization. It is because when Potassium has reached resting value, some Potassium channels are still open and Potassium efflux continues, resulting into more negative membrane potential. (1 mark)

Q.4 What is the mechanism of action of post-synaptic neuro-muscular transmission blockers? Classify them with examples & give their uses. (1+3+1 mark) KEY: MECHANISM: They do not interfere with release of Acetylcholine but antagonize with action of Acetylcholine. (1 mark) Classification: 2 types: 1. Competitive: Compete with acetylcholine to bind with acetylcholine receptors on motor end plate as they are given in large doses no depolarization, no E.P.P Muscle relaxes. (0.5 mark) Examples: (1 mark) Snake poisons (alpha Bungaro toxin in snake venom), Synthetic (Flexidyl or Galamine used in O.T) and Natural (Detubo-curarine). 2. Depolarizing: Resemble acetylcholine in action. They bind with receptors

depolarization of persistent nature. Only 1 nerve impulse is transmitted initial twitching of muscle. (0.5 mark) Examples: (1 mark) Suxamethonium, Decamethonium and Hexamethonium. USES: (1 mark) 1. Muscle relaxant in surgery. 2. Has been used in Psychotic patients in electro-convulsive therapy.

Q. 5 Give five differentiating features between unitary & multiunit type of smooth muscle. (5 marks) KEY: 1 mark for each. 1. 2. 3. 4. 5. LOCATION TYPE OF JUNCTIONS ARRANGEMENT CONTROL ACTION POTENTIAL.

1. LOCATION: UNITARY: Wall of GIT, ureter, bile duct, uterus and large blood vessels. MULTIUNIT: Ciliary muscle of eye, Iris of eye and pilo-erector muscle. 2. TYPE OF JUNCTION: UNITARY: Diffuse junction. No contact with nerve fiber. Neurotransmitter is released near the fiber. MULTIUNIT: Contact junction.One of the autonomic nerves form junction with muscle fiber and releases neurotransmitter like nor-epinephrine. 3. ARRANGEMENT: UNITARY: Sheaths or bundles with gap junctions in between, so act as single unit. If one part is excited whole is excited. MULTIUNIT: Individual muscle fibers. Each fiber has insulating outer membrane with glycoprotein and collagen consistency. Independently each muscle fiber is excited. 4. CONTROL: UNITARY: Mainly non-nervous stimuli (hormonal stimuli like oxytocin and serotonin). Show spontaneous contraction. MULTIUNIT: Mainly through nervous stimuli. Does not show spontaneous contraction. 5. ACTION POTENTIAL: UNITARY: 3 types: Spike, Plateau and Slow wave. Rhythm due to increased or decreased pumping of sodium. MULTIUNIT: Not required as individual muscle fibers are too small to produce action potential. Only localized depolarization in response to excitation.

Q.6 Key:

Two different patients present with arterial PH of 7.6 & 7.4 respectively. In which case tetany may be aggravated more easily & why? (1+4 marks)

In the first case (alkalosis), tetany is aggravated. (1 mark) Because protein molecules behave as acid in alkaline pH and can donate H and become anions which bind positive ions (Na, K, Ca) (1 mark) protein bound form of Ca increases & ionic form decreases (1 mark) decreased Ca in ECF no complete closure of activation gates of Na channels at rest. (1 mark) Na ions leak into membrane from ECF Hypopolarization (Membrane potential becomes less negative and near to threshold) & on slight stimulation action potential e-g., Tetany. (1 mark) Q.7 A 30 year old lady complained of double vision (diplopia), severe muscle weakness & fatigue. She has drooping of eyelids and an enlarged shadow of thymus on ultrasound. a. b. c. d. What can be the possible diagnosis of this disturbed physiology? What is the physiological basis of this pathology? What positive finding do you expect in her serum examination? What medicine can alleviate the ladys complaints? (1+2+1+1 mark)

Key: a. MYASTHENIA GRAVIS (1 mark) b. A rare auto-immune disease. Irreversible damage to acetylcholine receptors at motor end plate, though acetylcholine is normally released. Voltage of EPP is very low (Miniature EPP) action potential is not followed. At rest normally, a few synaptic vesicles break to liberate Ach from synaptic vesicles small change in EPP (about 0.5 mV) called MEPP. Impulse fails to transmit through NMJ Severe muscle weakness & fatigue (Extraocular muscles ptosis, diplopia, difficulty in Swallowing, weakness of Respiratory and Facial muscles) (2 marks) c. AUTO-ANTIBODIES against acetylcholine gated receptor channels. (1 mark)

d. ANTICHOLINE ESTERASES (Neostigmine or Physostigmine). These inhibit enzyme acetylcholine esterase acetylcholine is not hydrolyzed more acetylcholine available for available number of receptors. (1 mark)

Q.8 Why ATP is required for muscle relaxation in an alive person? Compare the onset of rigidity after death incase of hot and cold environmental temperatures. Why this rigidity disappears 24 hours after death? What is the scientific name for rigidity after death, give its forensic significance? (1+1+1+2 marks) KEY: Calcium pump needs ATP to pump back calcium into terminal cisternae muscle relaxation by detachment of cross-bridges of myosin from actin. (1 mark) Rapid onset incase of hot weather and slow incase of cold. (1 mark) Due to autolysis of muscle proteins, resulting from hydrolytic enzymes from lysosomes. (1 mark) RIGOR MORTIS. Cause of death by a weapon incase of suicide, as the weapon remains in the rigid hand as contracture develops soon after death and lasts for 16-24 hours. It also gives some estimate of the number of hours elapsed since death. (2 marks)

Q.9 Give a brief account of fast and slow muscle fibers. Key Every body muscle is a mixture of fast & slow muscle fibers. Also are present intermediate fibers in between them.

(5 marks)

Significance of fast fibers: Muscles that react rapidly are mainly composed of fast fibers, with only few slow muscle fibers. Significance of slow fibers: The muscles that respond slowly & have a prolonged contraction, mainly consist of slow fibers. (1 mark)

Fast Vs Slow muscle fibers:

Fast / Large fibers. Great strength of contraction. Extensive sarcoplasmic reticulum (to supply calcium for contraction). Less blood supply (oxidative metabolism is of secondary importance) Fewer mitochondria (only secondary importance of oxidative metabolism). White muscle due to lack of myoglobin. Motor unit smaller. Richer nerve supply. Slow / Smaller fibers. Innervated by smaller nerves.

Richer blood supply to supply extra amount of oxygen.

Increased no. of mitochondria for high level of oxidative metabolism. Increased myoglobin to store oxygen. Red muscle due to myoglobin. Motor unit larger.

(4 marks)

Q. 10 Compare 3 types of muscle.

(5 marks)

F rom Saladin

SKELETAL MUSCLE

CARDIAC MUSCLE

SMOOTH MUSCLE

SKELETAL MUSCLE Voluntary Cross-stria d te Cross-striate

CARDIAC MUSCLE Involuntary Cross-stria d te Cross-

SMOOTH MUSCLE Involunta ry

Individua skeleta l l m uscle ce is a ll m uscle fiber.

Hom ne oge ous cytoplasm no , cross-striations crossIndividua ca c l rdia 1. Viscera Unitary : l/ Visceral/ ce is not a m ll uscle she ths or bundles a fiber, but connecte act as a single unit. d a fibe r, ct in series to form a 2. Multi-unit type: : Multitype m uscle fibe r. fiber. Individua m l uscle ce is a m ll uscle fiber. fibe r. Gap junctions Ga p 1. Ga p. 2. Conta ct.

No ga junctions p gap

SKELETAL MUSCLE Multiple peripheral periphe ral nuclei. nucle i. Tria is at the d junction of A & I ba nds.

CARDIAC MUSCLE Single ce ntral nucleus. Intercalate discs / Inte la d rca te ga junctions a at p re the leve of Z l level m brane (Dia ) em nes. (Diad d) s.

SMOOTH MUSCLE Single centra ntral l nucleus. nucle us.

In som pla s e ce (intestine ra ), ndom ly distribute thick & d thin filam nts fila e m interdigitate te. . Few m itochondria . mitochondria More m itochondria Fewer Fewe r Major source of energy (25% m ss). Ma Ma jor itochondria . a Major m jor is CHO. source of e nergy is Mostly glycolytic Glycolysis Citric a cid fat (60%) a re t st. m ta e bolism . fa t at rest.
cycle .

SKELETAL MUSCLE Multiple peripheral periphe ral nuclei. nucle i. Tria is at the d junction of A & I ba nds.

CARDIAC MUSCLE Single ce ntral nucleus. Intercalate discs / Inte la d rca te ga junctions a at p re the leve of Z l level m brane (Dia ) em nes. (Diad d) s.

SMOOTH MUSCLE Single centra ntral l nucleus. nucle us.

In som pla s e ce (intestine ra ), ndom ly distribute thick & d thin filam nts fila e m interdigitate te. . Few m itochondria . mitochondria More m itochondria Fewer Fewe r Major source of energy (25% m ss). Ma Ma jor itochondria . a Major m jor is CHO. source of e nergy is Mostly glycolytic Glycolysis Citric a cid fat (60%) a re t st. m ta e bolism . fa t at rest.
cycle .

SKELETAL MUSCLE Spike potentia ntial. l. (Am plitude up to 120 m V). Quick tra ission nsm of im pulse a long sa rcolem a m. sarcolem a. Less dura tion duration of contra ction. ATPasea sea ctivity not so slow.
Ca be tetanized. Shorte n nize d. r re ctory pe fra riod. (2refra period. (2-3 millisec) illise c)

CARDIAC MUSCLE Action pote l ntia with platea pla u. tea (Up to +20 m V overshoot). ove rshoot). La m tch nism . Latch echa Prolonge d contra ction. Slow ATPa se activity in Myosin head. a d.
Cant be teta d. n nized. Longer R.P. (300 milli-se illi- c)

SMOOTH MUSCLE Viscera 3 types of l:

a ction potentia l: Spike, pla a & slow te u wa (rhythm due to ve increa or decreased sed decrea sed pumping of sodium ). Slow transmission. nsm ission. Prolong contra ction. Multi-unit: loca lized Multi-unit: depola tion. Sm ll riza a fibers, Ac.Pot. not reqd. Ac.Pot. (Up to 60 m V). mV).
Viscera Refra l: ctory pe riod period is m tha in Skeleta ore n Skele l ta m uscle.

SKELETAL MUSCLE One m uscle fiber is a syncitium. . syncitium Single fiber obeys All or none la w. No autom aticity. No rhythmicity icity. .

CARDIAC MUSCLE Functional Functiona l syncitiuma a s syncitiuma whole. As a whole obe ys obeys All or none la w. Automaticity & a ticity Rhythmicity icity. .

SMOOTH MUSCLE Viscera like Cardiac l: Cardia c Muscle . Multi-unit: like Multi-unit: Ske ta Muscle le l . Viscera Show l: spont. contrac. c. spont. Stre & re ss verse stress relaxation. rela xation. Multi-unit: Nervous. Multi-unit: Not sponta neous.

SKELETAL MUSCLE Less myoglobin. yoglobin. Less glycoge n. Less blood supply. Exa ple m s: Muscles covering cove ring the bone of lim s bs. bones

CARDIAC MUSCLE

SMOOTH MUSCLE

More myoglobin. yoglobin. Inte e te rmedia . Interm diate. More glycoge n. More blood supply. Exam Exa ple: m He m art uscle in thorax. Exa ple m s:
Viscera l: Visceral: . Wall of GIT, ureter, ureter, bile duct, uterus, large Blood Vessels la rge Multi-unit: MultiCiliary m uscle, iris, pilo-erector. pilo-

11. Short notes: a. Summation of synapse b. Post tetanic facilitation.

(2.5 +2.5 marks)

2 TYPES OF S UMMATION:
TEMPORAL Impulses tra nsm through 1 it or few syna knobs ptic synaptic repea tedly effects on postpostsyna neurons a a d ptic re dde stimula stim tion. ula Second stim ulus ust ll stimulus m fa when effect of 1st one is still there. JO PATHAR PAY PANI PARAY MUTTASIL, TO BAY SHUBA GHIS JAAY PATHAR KI SIL! SIL!

SPATIAL Im pulse are conducte sa d re along a numbe of ber r syna pses sim ne ulta ously e ffects on postsynaptic ne uron a re adde e d xcita tion. MOUJ HAY DARYA MEIN OR BAYROON A DARYA KUCH NAHIN!! NAHIN!!

b. Post tetanic facilitation.

POS -TETANIC FACILITATION T OR POTENTIATION:

(Ret isb s fo tet!) s et r st!) If im pulses are conducte through a synapse ra d pidly a re the re is give to syna the aga impulses a n st n pse then in pulse re n s conducte re d sponse of post-synaptic neuron is postincre se ased. d. Ca lcium nter ptic ach Calciumions ente in syna knob in ea r ch tra ission, before fa nsm tigue occurs increaseno. of a se transm ca lcium accumulatein knob m neurotransm ula ore neurotra itter a ccum te nsm re ase m EPSP. le d ore EPSP. After fa tigue n ore calciumions lcium fatigue if rest is give m ca re st given be e a ila facilitation. com va ble cilita tion.

12. Write a note on Wallerian Degeneration. Changes in distal stump of injured nerve:

(5 marks) (2 marks)

Axon & myelin sheath completely degenerate (secondary / Wallerian degeneration). Simultaneous degeneration throughout length of nerve fiber. Changes appear in 24 hrs & complete in 3 wks. Continued conduction for 3 days post injury. After 5th day all function is stopped.

HISTOLOGICAL CHANGES IN DEGENERATION OF NERVE: Axoplasm breaks up into short segments. Swelling of neurofibrils become tortuous & disappear after sometime. Within few days, space containing axoplasm shows only a little debris. Myelin sheath disintegrates fat droplets appear (8th to 32nd day). Lecithin molecules present in myelin sheath completely hydrolyzed to glycerol, fatty acids, phosphoric acid & choline removed by increased number of macrophages (appearing as foam cells due to their high lipid content) or by blood stream. Endoneurium remains intact within endoneurial tubes. Schwann cells proliferate & their increased number along with fibrous tissue false neuroma. (True neuroma in regeneration) (3 marks)

Q. 13 Define REFRACTORY PERIOD and its types. What is its mechanism? Give the normal value of ABSOLUTE REFRACTORY PERIOD of skeletal muscle? (2+2+1 mark) Key: Definition: During the local response, threshold is lowered, but during the rising & much of the falling phases of spike potential, neuron is refractory to stimulation. This is called refractory period. Mechanism: Ionic basis is given: 2 types: Absolute: During depolarization & first 1/3 of repolarization. Here sodium inactivation gates are still closed & will not open till potential reaches resting value. Relative: From end of first 1/3 of repolarization to the beginning of after depolarization. (here stronger stimulus can produce action potential). Normal value of absolute refractory period of skeletal muscle: 2-3 msec. (Normal value of absolute refractory period of ventricular muscle: 200-300 msec) Q.14 A hyperventilating young girl of 20 years reports to her physician with a typical position of the hand at the wrist due to spasm of muscles. An I/V injection of a calcium salt results in remarkable improvement of the girls condition. a. What is the technical name given to this condition of the girl? b. Why was calcium so effective? c. What is the role of calcium in muscle contraction? (1+2+2 marks) Key: a. TROUSSEAUS SIGN: A spasm of muscles of the upper extremity that cause flexion of the wrist & thumb with extension of fingers. It is a sign of tetany. b. Sign of Tetany was manifested due to hypocalcemia. Hypocalcemia increased excitability of nervous tissue. Calcium (normal levels) stabilizes the membrane: Inner side of sodium channels is highly negatively charged. Calcium ions from ECF bind with negative inner surface of sodium channels complete closure of activation gates of these channels at rest. Decreased calcium in ECF no complete closure of activation gates of sodium channels at rest sodium ions leak into membrane from ECF hypo-polarization (membrane potential becomes less negative & near to threshold) & on slight stimulation action potential (tetany).

c. Calcium is needed by skeletal muscle for coupling of excitation with contraction. Action potential enters deep into muscle fiber from T-Tubules around which are terminal cisternae. So depolarization spreads from T Tubules terminal cisternae. Membrane of terminal cisternae is depolarized opening of voltage gated calcium channels calcium ions move into terminal cisternae.

When it is in sarcoplasm, calcium is utilized by troponin C to initiate muscle contraction (excitation-contraction coupling). 4 calcium ions can bind with 1 molecule of troponin C it breaks the bond between troponin I & Actin tropomyosin strands become loose they reach a deeper position active sites on actin are uncovered Muscle contraction involves power strokes. Before contraction, a molecule of ATP becomes attached to myosin head. It is hydrolyzed to ADP to liberate energy stored in myosin head. When active site is uncovered myosin head binds with active site on actin. With stored energy, there is power stroke. At hinges, myosin molecule moves & carries along actin / thin filaments Contraction is initiated by calcium ions. As long as calcium ion is sufficient in sarcoplasm muscle contraction continues. Q.15 How is RMP generated? (5 marks)

Key: Potential difference across cell membrane at rest: Inside negative with respect to outside. Potential values vary: In nerve fiber: -90 mV In skeletal muscle: -90 mV In cardiac muscle: -85 mV In nerve cell body: -70 mV In smooth muscle: -55 mV to -60 mV

Me chanism of re gulation of RMP:

K+ OUTSIDE Na +

4m / L Eq 140 mEq / L INSIDE

140 mEq / L 14 m / L Eq

Na IS 10 TIMES > OUTSIDE THAN INSIDE + SO K+ IS 35 TIMES > INSIDE THAN OUTSIDE TEND TO DIFFUSE OUT & Na WILL TEND TO DIFFUSE IN. + INSIDE CELL MEMBRANE ARE PROTEIN CHANNELS (LEAK / VOLTAGE / LIGAND GATED) K+ , Na LEAK CHANNELS ARE 100 TIMES MORE PERMEABLE + PERMEABLE TO K+ THAN TO Na (AT REST MORE K CHANNELS ARE OPEN THAN Na +. ) SO MAIN MOVEMENT IS K+ OUTFLUX WHICH CONTRIBUTES TO RMP (ne tive inside) ga inside )
K+ WILL

Me chanism of re gulation of RMP (continue d)

+ Another fa ctor is Na - K + pum (a p ctive all the tim e). + Pum out 3 Na ions & ps Pum in 2 K + ions. ps So m e ctro-positive ions a pum d out & ore lectrore pe contribute to RMP. s As m m ne is m perm a to K + a re & m e bra ore e ble t st, uch ionic diffusion, so large am ove larg e ount of K + should m out, but net m e uch. Why??? ne ovem nt is not m t

This is because when K+ moves out, anions (non-diffusible: proteins, organic phosphate & organic sulfate anions) attract them back. But this movement is sufficient to cause relative electro-negativity inside the membrane. Out of -90mV, -86mV is due to K+ outflux & -4 mV is due to Na+ K+ pump. What is the evidence??? Evidence of major contribution to RMP by K+ ion: If we change, [K+] in ECF RMP is disturbed. If there is hypo-kalemia in ECF RMP will become more negative due to more potential difference hyper-polarization (more K+ leak out than resting level more negativity on inside). If there is hyper-kalemia RMP becomes less negative (less K will leak out due to less potential difference) hypo-polarization (less negativity on inside). But changes in [Na+] in ECF no significant effect on RMP. We can also prove this by Nernst Equation. Nernst Equation: EMF (mV) = +/- 61 log conc. inside / conc. outside Assume that at rest, cell membrane is highly permeable to Na+, then: -61 log 14/140 (-)for Na+ & K+ & (+) for Cl-) = -61 log 0.1 = -61 x -1 = + 61 mV So potential difference across cell membrane should be +61mV, which is wrong.

Assume that at rest, cell membrane is highly permeable to K+, then: - 61 log 140 / 4 = -61 log 35 = -61 x 1.54 = -94 mV (close to RMP) So this assumption is correct that at rest, cell membrane is highly permeable to K+.

Goldman Hodgkin-Katz Equation:

Goldman Hodgkin-Katz Equation:

EMF (mV) = (m V) - 61 log C Na+ i P Na+ + C K+ i

P K+ + C Cl- o P Cl-

C Na+ o P Na+ + C K+ o P K + + C Cl- i P ClNa + K+

(C = CONCENTRATION, P= PERMEABILITY)

WITH GOLDMAN EQUATION SUMMATED POTENTIAL = -8 m 6 V

K+ Na+ leak channels are highly permeable to K+ but there is some inward movement of Na+ + 8 mV potential is generated. -94 mV is due to K+ efflux + 8 mV is due to Na+ influx -94 + 8 = -86 mV = Goldman potential -4 mV is due to Na+ K+ pump -86 4 = -90 mV = RMP. Q.16 Define CHRONAXIE. How is an action potential propagated along a myelinated nerve fiber? (5 marks) Key: CHRONAXIE: A time for which a stimulus, double the rheobase when applied, just excites the tissue, e.g., 2 mV. (Chronological is from time, so chronaxie is a unit of time). (1 mark)

Propagation of action potential along a myelinated nerve fiber:

(4 marks)

Node to node conduction. Also called saltatory / jumping conduction. All channels are present at nodes of Ranvier. Myelin sheath is absent & only neurilemma is there at the node.

Local circuit of saltatory conduction: Polarized node adjacent depolarized node through axoplasm polarized node.

Com parason of velocities in 2 types of fibers:

Myelinated

Unmyelinated

120 m/sec (fast)

Thicker nerve fiber = longer internode = greater velocity e.g A-alpha fibers Less energy expenditure due to less ionic change as internodes are not being used, only nodes are used.

2-5 m/sec

Q.17 Draw & label the NMJ. Enumerate various events involved in neuromuscular transmission. (5 marks) Key: Diagram: (1 mark)

Events: Nerve impulse nerve terminal depolarization of membrane of nerve terminal opening of voltage gated calcium channels in membrane. Calcium (ECF) End foot / nerve terminal agitation of some of the synaptic vesicles (125 -150 vesicles become agitated & fuse with membrane) break their acetylcholine into synaptic cleft by exocytosis. Ach (released) binds with receptors (part of protein molecules) at motor end plate (Ach gated channels/ cholinergic receptors/ ligand gated channels) of nicotinic type at motor end plate opening of Ach gated channels sodium influx EPP (localized potential change). It is graded (amplitude is directly proportional to amount of Ach released). Not self propagated, so decrease with distance. Prolonged in duration. Because of EPP Threshold for action potential is reached (-65 mV). If RMP is -90 mV, then threshold is -65 mV, we need 25 mV potential change. Purpose of EPP is to reach the threshold of action potential. So voltage of EPP is much more than required, because required is only 25 mV. It is called SAFETY FACTOR.

 Recycling Ach once released, remains bound with receptors only for 1 msec. Some diffuses out to ECF & rest is hydrolyzed by enzyme acetylcholine esterase of sub-neural cleft. Ach (on hydrolysis) Choline + Acetate So that new impulse can be transmitted through NMJ. These channels have 5 sub-units: 2 alpha sub-units which protrude out on surface & 3 others are beta, gamma & delta. Ach synthesized in synaptic knob vesicle released recycled. Mitochondria energy Ach formation from CoA & Choline synaptic knob. Impulse reaches agitation of vesicles Ach binds with receptors Ach esterase acetate & choline recycled. Q.18 Draw & label Action Potential of nerve fiber. List all of its components & give the ionic basis for each of these. Define After depolarization & After hyperpolarization. (2+1+2 marks)

P eak +35 to 40 mV (O vershoot) 0 mV D epolarization [R apid A bsolute R efractory period [N + inactivation gates are still closed] a (F irst 1/ 3repolarization of )

R epolarization [K+ efflux] M em brane V oltage+ R elative R efractory period N ainflux ] (70% of repolarization of / start (m V ) Spike potential A fter epolarization) -D Slow / K +accumulate T hreshold mV C om plete -65 -65mV R epolarization E xcitable/ -normal period Super opening of + A fter epolarization D fast N achannels R M P mV -90 R M P mV -90

T im e (m s)

A fter H yper -polarization (U ndershoot) -normal period (mV ) / Sub -95 + efflux continues, K + channels remain [K open for som e tim e after R M P is reached]. H ere tissue is difficult to be excited.
Action potential Graph: (2 Marks)

x-axis: Time in milliseconds (0.25 mV) y-axis: Voltage in millivolts (0.25 mV) RMP: - 90 mV (0.25 mV) Threshold: - 65 mV (0.25 mV) Peak: +35 to 40 mV (0.5 mV) Phases: Depolarization (upstroke), Repolarization (downstroke), Hyperpolarization (negative, below the baseline) (0.5 mark) Note: If ionic basis is mentioned on the graph, then it is not needed in the text.

STAGES & IONIC BASIS: Resting Membrane Potential (-90 mV) is due to tendency of potassium ions to move out of the interior of nerve fibers. At this stage conductance for potassium ions is 50100 times as great as conductance for sodium ions greater leakage of sodium ions through the leak channels. (0.25 marks) Depolarization phase starts from threshold value (-65 mV), when all the sodium gates / channels open up sodium influx. It ends at the peak level (+35 to 40 mV). (0.25 mark) Repolarization phase starts at the peak (+35 to 40 mV) and ends at the baseline (RMP = - 90 mV). It is due to potassium efflux (potassium gate is open). (0.25 mark) Absolute refractory period includes depolarization and first 1/3 of repolarization. Sodium inactivation gates are still closed and will not open till potential reaches resting value. (0.25 mark)

During repolarization, Potassium becomes accumulated on outer side of membrane which slows down further efflux after 70% of repolarization leading to slow repolarization called After depolarization. (1 mark) When potential has reached the resting value, it does not stay there and becomes more negative and called After hyperpolarization. It is because when Potassium has reached resting value, some Potassium channels are still open and Potassium efflux continues, resulting into more negative membrane potential. (1 mark)

Q. 19 What is LATCH PHENOMENON in a smooth muscle fiber? What is its importance & how is it regulated? (2+1+2 marks) key: Smooth muscle can maintain prolong contraction with expenditure of small amount of energy LATCH MECHANISM. Importance: It can maintain prolong tonic contraction in smooth muscle for hours with little use of energy. Little continued excitatory signal is required from nerve fibers or hormonal sources. Once smooth muscle has developed full contraction, the amount of continuing excitation usually can be reduced to far less than the initial level, yet the muscle maintains its full force of contraction. The energy consumed to maintain contraction may be as little as 1/300 the energy required for comparable sustained skeletal muscle contraction. Regulation: When myosin kinase & myosin phosphatase enzymes are both strongly activated, the cycling frequency of myosin heads & velocity of contraction are great. As the activation of enzymes decreases, the cycling frequency decreases, but at the same time, the deactivation of these enzymes allows the myosin heads to remain attached to the actin filament at any given time remains large. (Slow ATPase activity of myosin head). Because of the number of heads attached to actin determines the static force of contraction, tension is maintained, or latched; yet little energy is used by the muscle, because ATP is not degraded to ADP except on rare occasion when a head detaches. Q.20 Define and draw a sarcomere. Enumerate changes which occur in it during muscle contraction. (2+3 marks) key: SARCOMERE: The structural & functional unit of muscle. The portion of myofibril between two successive Z lines. (0.5 mark) Diagram: see under changes.

Histological change during muscle s contraction:

RELAXED MUS CLE :

AFTER CONTRACTION :

2-2.5 m length of sarcomere rcom . ere.

1-1.5 m length of sa rcomere ere. . Length of A ba consta nd nt. Length of I ba (Actin nd band (Actin filament on either side of Z m ent line, not covered by Myosin) decrea ses. Z Membra becom closer. e Mem nes bra H zone decre ses / disa a ppea r Sliding of thin over thick filaments. m ents. Length of individua l filaments rema the sa e. m ents rem in m a (3 marks)

(1.5 marks)

Q.21 How is action potential propagated along a myelinated nerve fiber? What are the advantages of this propagation? (5 marks) Q.25 What is salutatory conduction? What are its advantages? Which nerve fibers have maximum velocity of conduction? (1+2+2 marks) Key: Propagation (saltatory conduction): (3 marks) See Q. 16 Advantages: (2 marks) i. It increases velocity of conduction directly in proportion to the fiber diameter, velocity of A alpha fibers = 120 meters/sec. ii. Conservation of energy- less energy expenditure. Q. 22 Define Rheobase & Chronaxie. Show these units in Strength-duration curve. (1.5+1.5+2 marks) Key: RHEOBASE: Voltage / strength of stimulus required just to excite the tissue, e.g., 1 mV. CHRONAXIE: A time for which a stimulus, double the rheobase when applied, just excites the tissue, e.g., 2 mV. (Chronological is from time).

Q.23 Draw & label NMJ. How is EPP produced? What change occurs in this potential in Myasthenia Gravis? (2+2+1 mark) key: See Q.17 & Q.1 Q.24 What is Compound Action Potential? Draw & label it. (3+2 marks)

Key: Multi-peaked action potential recorded from a nerve. For example: Sciatic nerve has number of nerve fibers of different diameters & different velocity of conduction. When action potential from different nerve fibers are recorded multiple peaks. 3 main peaks: A, B, C. A is further divided into alpha, beta, gamma, delta. A & B types are myelinated & C type is unmyelinated. Compound action potential is basis of physiological classification of nerve fibers. A alpha fibers with maximum diameter have highest velocity of conduction, up to 120 m/sec.

Even lower most graph is enough.

Q.26 Compare the features of Isometric & Isotonic types of skeletal muscle contraction. (5 marks) key:

TYPES OF CONTRACTION
ISOTONIC (same tone) Muscle length decreases but muscle tension constant. Work is done in this type of contraction. Example: lifting of book from a table.
(1 mark each point = 3 marks)

ISOMETRIC (same length) No appreciable change in length of muscle but muscle tension increases. Work is not done. Example: heavy weight balancing by weight lifters and body builders.

Isotonic

Isom tric e Isome

Isotonic

Muscle shortens, tension remains constant Movement occurs

Muscle develops tension but does not shorten No movement

Isom etric

Body move nts are a mixture of isotonic and isome me tric moveme m nts. e In muscle 2 types of elem ents: m uscle 1 Contractile e ments ) le nts: : (thin/ a & thick/ m ments) thin/ ctin thick/ yosin fila 2 Elastic e m nts: ) le ents : (tendons & sa rcolem a ends of m ml uscle fibers a ched to tendons) tta Ela com stic component is in series with contra ponent ctile component. Contractilecom ponent undergoes shorte ning & Contractilecom e lastic component undergoes stretching tching. . com ponent

Muscle must shorten 3-5% extra to neutralize e xtra neutra lize the stre tching of ela component. e stic la In isom tric exe e rcise only 3 5% muscle , isome shorte ning, tendons a stretching & this re shorte ning neutra s the stre lize tching no cha in le nge ngth.

 Significance: Isometric contraction is used to compare the functional characteristics of different muscle types including Fast and Slow Muscle Fibers . (0.5 mark) Body movements are a mixture of isotonic and isometric movements. (0.5 mark)

Q.27 When sciatic nerve is electrically stimulated, which type of potential record is obtained? Draw & explain it. (5 marks) COMPOUND ACTION POTENTIAL is produced. Diagram: See Q. 24

Q.28 How is impulse conducted from a nerve to muscle fiber? What is myasthenia Gravis? (3+2 marks) Key: See NMJ Q.17 Myasthenia Gravis: A rare auto-immune disease. Voltage of EPP is very low (Miniature EPP) action potential is not followed. At rest normally, a few synaptic vesicles break to liberate Ach from synaptic vesicles small change in EPP (about 0.5 mV) called MEPP. Amplitude varies directly with [Ca++] and inversely with [Mg++]. Impulse fails to transmit through NMJ Severe muscle weakness & fatigue (Extra-ocular muscles ptosis, diplopia, difficulty in Swallowing, weakness of Respiratory and Facial muscles)

EPP Vs AP

EPP: Loca potentia recorded only l l a End pla region. t te Volta 0.5 m (MEPP) ge: V EPP va with strength of ries stimulus / am stim ulus mount of ount neurotransm nsmitter relea sed. itter Can show summa m tion. a Ca n

AP: Self-propa ted. ga SelfVolta 35-40 m ge: 35 V

AP follows All or None La requires only threshold w/ stim ulus. Does not show summ tion. sum a ma

Auto-a re d aga gainst ted Auto- ntibodies a produce a inst Ach gate are d rece ceptor channe & the re ptors a destroye ls se ce re ptor are stroyed d irreversibly though Ach is present (pove amongst versibly, , se (pove nt rty ple nty/ havethemone but pizza shop is close y, d / all dre d up but no placeto go!). sse ). go! TREATMENT: Anticholineestera s (Neostigmine se ine, , TREATMENT: Anticholineesterases Physostigmine m rke im ine) ) a d provem nt. e Adrophoneuminjection: (short acting a choline Adrophoneuminjection: a cting nti este se e rase stera ) Me nism of action: anticholinee ra s inhibit cha a ction: anticholineeste se stera enzym cholinee e sterase Ach not hydrolyzed se e nzym cholinee hydrolyze d m Ach a ila for a ila num r of receptors. ore vailable blefor va ble be re ceptors.

Evidence of autoimmune disease: Auto antibodies detected in patients blood. In many of these cases, thymus is enlarged & thymectomy is of benefit. If mother is myasthenic, newborn shows features of myasthenia for few weeks because antibodies cross the placenta. But antibodies die in few weeks, due to limited life span. They will destroy few receptors, which will regenerate later.

Q.29 Differentiate between a graded potential & action potential. (5 marks)

EPP Vs AP

EPP: Loca potentia recorded only l l a End pla region. t te Volta 0.5 m (MEPP) ge: V EPP va with strength of ries stimulus / am stim ulus mount of ount neurotransm nsmitter relea sed. itter Can show summa m tion. a Ca n

AP: Self-propa ted. ga SelfVolta 35-40 m ge: 35 V

AP follows All or None La requires only threshold w/ stim ulus. Does not show summ tion. sum a ma

OR the following question may be asked: EPSP Vs Action Potential

EPS Vs ACTION POTENTIAL: P Table 2 4Mushtaq EPSP

Low

Prope rty Property

Ma gnitude Propa gation & Dura tion Refra ctory pe riod period All or none la w

Action Pote l ntia Potentia

High

Nil; rem ins localize 20 Self propa a lized, gating d, m sec 2m sec a bsent Not obeye size dire d; ctly obeyed; proportiona to intensity l of stim ulus Present Pre sent pre nt se prese obeyed obeye d

Decrement (decline of e nt size with dista nce)

Absent; size is a ys the lwa sa e m Na first, then K+ +

Incre sed perm bility to To Na & K+ a one a ea + t ions tim but Na influx is e + m grea than K+ uch g te rea efflux

Q.30 Which record is obtained when a nerve trunk is stimulated? Draw and explain this record. (5 marks) Key: Compound Action Potential See Q. 24

Q.31 How is MYELIN SHEATH formed in the peripheral and central nervous system? What are its functions? (2+3 marks)

Mye linogene nesis sis

Forma yelin shea a th round the a xon. Form tion of m a In periphera nerve, it sta a 4th I.U m l nerve , rts t onth. It is completed in 2nd ye r a birth. a com pleted yea fter Myelin shea is produced by la th yers of Schwann cells. Schwa nn Outerm la of Schwa cells rem in a neurilem a/ ost nn a s mma/ Outermost yer rema as m Shea of Schwa th nn. Cytopla of Schwa ce is not deposited. sm nn lls Nucleus of Schwann cells rema between neurilem a& myelin ma& Schwa nn rem in a shea It is fla th. ttened ted. flattened & elonga 1 nucleus a ea inter-node of a t xon. at ch interSchwa n cells a a bsent in CNS. CNS. Neurilemm is a ais Neurilemma bsent in CNS. In CNS OLIGODENDROGLIA MYELIN SHEATH. In PNS SCHWANN CELLS MYELIN SHEATH. SHEATH.

Functions: FASTER CONDUCTION: Saltatory / jumping HIGH INSULATION: Prevents stimulation of neighboring fibers. Q.32 An unidentified dead body was found in a street. The dead body was having rigidity. It was handed over to the police. After about 24 hours, rigidity of the dead body had disappeared. a. Why was the dead body having rigidity and what is that condition called? b. Why did the rigidity disappear? (3+2 marks) Key: a. Several hours after death muscles of dead body become rigid rigor mortis. After death ATP not available no detachment of cross-bridges of myosin from active site of actin filaments contracture / rigidity. b. After about 24 hrs rigor mortis disappears due to autolysis of muscle proteins (resulting from hydrolytic enzymes from lysosomes).

Significance: (CAN BE MENTIONED) Forensic significance: Cause of death If suicide has been committed, the gun or dagger is locked in the hand. Duration of death Some idea. Within 16 hrs of death, rigor mortis remains. It disappears after 16-24 hrs of death. Q.33 Which types of muscle contraction predominantly occur in a body builder during his performance and a Tennis player during his play? Compare the features of these types of contraction. (5 marks) Key: Isometric contraction in body builder while weight lifting in a stationary position. Isotonic contraction in tennis player during his play. See Q.26 Q.34 Briefly explain the factors responsible for generation of RMP. What do you understand by Nernst potential. How does it explain the equilibrium across the cell membrane? (2+1+2 marks) Key: See Q.15 Q.35 Classify the nerve fiber according to their diameter and conduction velocity. List the differences between EPP & Action Potential in a muscle fiber. (3+2 marks) key:

Classification by sensory physiologists:

Ia/ A alpha Ib / A alpha II /A beta III /A & gamma delta IV / C

Fibers from Fibers from annulospiral golgitendon golgitendon endings of organs. muscle spindles.

Fibers from Fibers carrying Unmyelinated cutaneousactile temperature, fibers carrying tactile t receptors & crude touch & pain, itch, flower spray pricking pain. temperature & endings of muscle crude touch. spindle. 17micron dia 16m in dia. 17micron 16 0.31.3m in Range1220m Range1220m 8 m in dia. : 3 m in dia. : Range & VelocityRange2-5 m dia V elocity :2 (beta ): Conduction Conduction velocity70120 velocity70120 5-12m, 3070 : : m/ sec m/ sec Conduction m/ sec Range & VelocityConduction Velocity: .5 V elocity 0.5 V elocity: 0 121(gamma: 36 m, Velocity: 230 2.3 m/ sec ): ) m/ sec 15-30 m/ sec 15

EPP Vs AP: See Q.29 Q.36 What is stress relaxation and reverse stress relaxation in a smooth muscle. List the events occurring during the propagation of action potential in an unmyelinated nerve fiber. (2+3 marks) key: Stress Relaxation: Smooth muscle can increase its size to accommodate increased volume, without significant increase in pressure /tension e.g we give massive blood transfusion to a person B.P increases but within few hours normal due to stress relaxation.

 Smooth muscle in vessel wall undergoes stress relaxation accommodate increased blood volume now even increased blood volume does not lead to increased blood pressure. Smooth muscle in stomach wall accommodate more food. Smooth muscle of urinary bladder (detrusor) can hold increased volume of urine. Smooth muscle of uterus can accommodate growing fetus. REVERSE STRESS RELAXATION: Smooth muscle contracts around the reduced volume no significant fall in pressure. e.g., in hemorrhage blood loss from body may cause shock but reverse stress relaxation of smooth muscle in vessel wall can prevent shock because it contracts around the reduced blood volume now even reduced blood volume adequately fills vascular system. Disparity between circulatory blood volume & capacity of vascular system is basic factor for shock. In neurogenic shock (vasomotor centre failure vasodilation) capacity increases but blood volume is same. This disparity cannot be compensated by reverse stress relaxation. Stress and reverse stress relaxation are due to loose arrangement of myosin & actin filaments which can adapt themselves to adopt a new size.

Propagation of action potential in un-myelinated nerve fiber: Point to point conduction. Local circuit of current is formed between depolarized point & adjacent polarized point.

Current flowing out through depolarized point, activates Na+ channels at polarized point depolarization action potential. Then a new circuit of current is formed between this depolarized point & adjacent polarized point.

This is point to point conduction of nerve impulse / action potential by forming local circuit of current between depolarized point & polarized point. In case of unmyelinated nerve fiber, velocity of conduction is slow, because it is point to point. Synapses only allow propagation between pre synaptic to post synaptic neuron inside the body, but in vitro it is in both directions. Q.37 Explain the events that occur when the motor nerve supplying a skeletal muscle is stimulated to produce the muscle contraction. (5 marks) key: Depolarization wave on sarcolemma transverse tubules of sarcoplasmic reticulum (1 mark) This in turn causes rapid opening of large numbers of calcium channels release of calcium. (1 mark) Calcium binds with Troponin C (1 mark) Displacement of Tropomyosin Active sites of actin are exposed. Hydrolysis of ATP at the head of Myosin ADP & Phosphate (1 mark) Power stroke: Myosin cross-bridges bend at hinges drag actin over myosin Length of sarcomere decreases contraction of skeletal muscle. (1 mark) Also draw diagrams: Fig. 7.6 & Fig. 6.4. (Guyton) Q.38 Write short note on: a. Rigor Mortis b. Myasthenia Gravis (2.5+2.5 marks) Key a. Several hours after death muscles of dead body become rigid rigor mortis. Its onset depends on: Temperature: increased temperature rapid onset. Activity: Vigorous activity of muscle before death rapid onset. Mechanism: After death ATP not available no detachment of crossbridges of myosin from active site of actin filaments contracture / rigidity. After 16-24 hrs rigor mortis disappears due to autolysis of muscle proteins (resulting from hydrolytic enzymes from lysosomes).

Key b. A rare auto-immune disease. Voltage of EPP is very low (Miniature EPP) action potential is not followed. At rest normally, a few synaptic vesicles break to liberate Ach from synaptic vesicles small change in EPP (about 0.5 mV) called MEPP. Amplitude varies directly with [Ca++] and inversely with [Mg++]. Impulse fails to transmit through NMJ Severe muscle weakness & fatigue (Extra-ocular muscles ptosis, diplopia, difficulty in Swallowing, weakness of Respiratory and Facial muscles)

EPP Vs AP

EPP: Loca potentia recorded only l l a End pla region. t te Volta 0.5 m (MEPP) ge: V EPP va with strength of ries stimulus / am stim ulus mount of ount neurotransm nsmitter relea sed. itter Can show summa m tion. a Ca n

AP: Self-propa ted. ga SelfVolta 35-40 m ge: 35 V

AP follows All or None La requires only threshold w/ stim ulus. Does not show summ tion. sum a ma

 Auto-antibodies are produced against Ach gated receptor channels & these receptors are destroyed irreversibly, though Ach is present (poverty amongst plenty/ have the money, but pizza shop is closed /all dressed up but no place to go!). TREATMENT: Anticholine esterases (Neostigmine, Physostigmine) marked improvement. Adrophoneum injection: (short acting anti choline esterase) Mechanism of action: anticholine esterases inhibit enzyme choline esterase Ach not hydrolyzed more Ach available for available number of receptors. Evidence of autoimmune disease: Auto antibodies detected in patients blood. In many of these cases, thymus is enlarged & thymectomy is of benefit. If mother is myasthenic, newborn shows features of myasthenia for few weeks because antibodies cross the placenta.

 But antibodies die in few weeks, due to limited life span. They will destroy few receptors, which will regenerate later.

Q.39 What is Walk-along theory & sliding filament model of skeletal muscle contraction? (2.5 + 2.5 marks)

Walk-along mechanism: Interaction between Activated Actin Filament and Myosin Cross-bridges Calcium ions activate actin filament. Heads of cross bridges from myosin filaments become attracted to active sites of actin filament contraction (walk along or ratchet theory of contraction). When a head attaches to an active site, the attachment simultaneous profound changes in intramolecular forces between head and arm of its cross-bridge. New alignment of forces, causes the head to tilt towards the arm & drag actin along with it. This tilt of head is called power-stroke. Immediately after tilting, head automatically breaks away from the active site. Head then returns to its extended direction. Head then combines with a new active site farther down along actin. Head then tilts again new power stroke & Actin moves another step. Thus heads of cross-bridges bend back and forth and step by step walk along the actin filament, pulling the ends of 2 successive actin filaments toward the centre of myosin filament.

Each cross bridge is believed to work independently, attaching & pulling in a continuous repeated cycle. So, greater the number of cross-bridges, in contact with actin, at any given time, greater is the force of contraction, theoretically.

Sliding filament mechanism:

\ Basic mechanism is shown in the figure of sarcomere in relaxed and contracted state. In relaxed state: ends of actin from 2 successive Z dics, barely begin to overlap one another. In contracted state: actin filaments have been pulled inward among myosin filaments their ends overlap to maximum extent. Also Z discs have been pulled by actin filaments up to the ends of myosin filaments muscle contracts by a sliding filament mechanism. This inward sliding is caused by forces generated by interaction of myosin cross-bridges with actin filaments. These forces are inactive at rest, but activate when action potential arrives calcium release from sarcoplasmic reticulum activation of forces between actin & myosin contraction. Energy for contraction comes from ATP ADP + energy.

Q.40 Compare the saltatory & non-saltatory conduction of nerve impulse. (5 marks) Key: 1. 2. 3. 4. Saltatory: in myelinated nerve fibers. Saltatory is fast conduction. It utilizes less energy. Velocity of conduction is directly Proportional to fiber diameter. A alpha fibers is an example. 5. Jumping conduction from one node to the next node. Local circuit of current is completed between depolarized node & adjacent polarized node. Current flowing through polarized node, activates sodium channels. Also draw diagrams for both . Non-saltatory in un-myelinated Slow conduction. More energy used. Pain / C fibers is an example Point to point conduction.

Q.41 Compare & contrast action potential / contraction of: a) Skeletal Vs cardiac muscle b) Skeletal Vs smooth muscle c) Cardiac Vs smooth muscle Key: See Q.10 Q.42 Briefly discuss in step wise manner general mechanism of muscle contraction. (5 marks) key: See Q.37 Q.43 Define & explain frequency summation & multiple fiber summation of skeletal muscle. (5 marks) key: Guyton pg 81 FREQUENCY SUMMATION: Draw fig: 6.13 Guyton At a low frequency: individual twitch contractions. At increasing frequency: each new contraction occurs before the preceding one is over. second contraction is added partially to the first total strength of contraction rises with increasing frequency. At a critical level of frequency: successive contractions become so rapid fuse together smooth & continuous whole muscle contraction tetanization. MULTIPLE FIBER SUMMATION: Weak signal from CNS to contract a muscle smaller motor units of muscle may be stimulated in preference to larger motor units. As strength of signal increases, larger and larger motor units begin to be excited as well, with larger motor units having 50 times the contractile force of smaller units (SIZE PRINCIPLE). Smaller motor units are driven by small motor nerve fibers & small motor neurons in spinal cord are more excitable than larger ones, so they are excited first. Different motor units are driven asynchronously by spinal cord contraction alternates among motor units one after the other, thus providing smooth contraction even at low frequencies of nerve signals. Q.44 See Q.37 Q.45 Draw fig: 8.4 Guyton. See Q.18 for figure of nerve fiber action potential