CHAPTER 6:

CONTRACTION OF SKELETAL MUSCLE

Compiled by: ABCJJKKP 2017

SYNAPTIC TRANSMISSION

SYNAPTIC TRANSMISSION
Electrical signals are transferred between neurons and sensory receptors or muscle cells. Synapses
Electrical Chemical

SYNAPTIC TRANSMISSION ELECTRICAL SYNAPSES

Low resistance Flow of current & exchange of small molecules Fast & bi-directional Low-pass filters No direct communication Presynaptic membrane axon Synaptic cleft 20-30 nm Postsynaptic receptors
Active zones

NEUROMUSCULAR JUNCTION
Specialized synapse between a motor neuron and a muscle fiber. Occurs at a structure on the muscle fiber motor end plate. (usually only one per fiber) Skeletal muscle fiber Neuromuscular junction Axons

NEUROMUSCULAR JUNCTION
Synaptic trough - Invagination in the motor end plate membrane. Synaptic cleft - 20-30 nm wide - Contains large quantities Of acetylcholinesterase. (AchE) Subneural clefts - Increase the surface area of the post-synaptic membrane - Ach gated channels at tops - Voltage gated Na+ channel in bottom half

THE MOTONEURON VESICLE FORMATION

Synaptic vesicles are formed from budding Golgi and are transported to the terminal by axoplasm streaming. (~300,000 per terminal)

NEUROTRANSMITTERS
Mediate chemical signalling between neurons Criteria: 1. Present in the presynaptic terminal & is synthesized by the cell. 2. Released on depolarization on the terminal 3. Specific receptors Major Categories 1. Small molecule transmitters 2. Peptides 3. Gaseous transmitters

NEUROTRANSMITTERS - CATEGORIES
1. Small molecule transmitters a. Acetylcholine (Ach) NMJ in the PNS b. Amino Acids (AA) Glutamate, Glycine & GABA in the CNS c. Biogenic Amines Dopamine, NE, E, Serotonin, Histamine d. Purines ATP 2. Peptides Fundamental in neurotransmission in the CNS a. Opiates & Opioids potent analgesics b. Substance P pain transmission in smooth muscle 3. Gas Neurotransmitters Nitric Oxide (NO), Carbon monoxide (CO)

ACETYLCHOLINE CYCLE
1. Acetylcholine is made from choline & Acetyl CoA. 2. In the synaptic cleft, Ach is rapidly broken down by the enzyme acetylcholinesterase. 3. Choline is transported back into the axon terminal and is used to make more Ach.

ACETYLCHOLINE EFFECTS
ACh receptors 2 a, 1 B, 1 d, 1 y proteins

EPP

50-70 mv

MUSCLE ACTION POTENTIAL

RMP : -80 to -90 mv in the skeletal fibers Duration: 1-5 msec Velocity of conduction: 3-5m/sec Threshold: -40mv

END PLATE POTENTIALS

Safety factor ratio of synaptic potential to the amplitude needed to reach threshold. Fatigue of NMJ
>100x/sec Failure of impulses to pass into the muscle fiber

WHICH OF THE FOLLOWING EPP IS A NORMAL END PLATE POTENTIALS?

DRUGS AFFECTING THE NMJ

Methacholine Carbachol Nicotine
Neostigmine Physostigmine Diidopropyl fluorophosphate - Can stimulate the MF - Not destroyed or slowly destroyed by cholinesterase - Persists longer - Inactivates acetylcholinesterase Ach muscle spasm

DRUGS AFFECTING THE NMJ

Curare plant toxins Curariform drugs Competes w/ Ach receptors Ach
Muscle membrane channels Na+ influx AP muscle contraction

MYASTHENIA GRAVIS
Autoimmune disease Igs (antibodies) block or destroy Ach receptors at the postsynaptic NMJ closed Na+ channels No depolarization Weak EPP Paralysis

EXCITATION CONTRACTION COUPLING

EC COUPLING THE TRIAD

The junction between two terminal cisternae and a T-tubule

EC COUPLING HOW IT WORKS

Sequence of Events
1. 2. 3. 4. 5. AP moves along T Tubule The voltage change is sensed by the DHP receptor Is communicated to the ryanodine receptor which opens (VACR) Contraction occurs Calcium is pumped back into SR. Calcium binds to calsequestrin to facilitate storage. Contraction is terminated.

6.

CLINICAL ODDITY: MALIGNANT HYPERTHERMIA

Symptoms Spontaneous combustion Skeletal muscle rigidity Lactic acidosis (hypermetabolism) Cause Triggered by anesthetics (halothane) Familial tendency can be tested for muscle biopsy Constant leak of SR Ca++ through ryanodine receptor Why is so much heat generated? Our bodies are only about 45% energy efficient. 55% of the energy appears as heat.

EC COUPLING CARDIAC MUSCLE

Sequence of Events
1. AP moves along T tubule 2. Activation of DHP receptors. - Voltage sensors that release a small amount of CA into the fiber. 3. Ca then binds to the ryanodine receptor which opens, releasing a large amount of Ca. (CACR) 4. Calcium is pumped (a) back into SR, and (b) back into T tubule. 5. Contraction is terminated.

EG COUPLING - COMPARISON
Skeletal Muscle 1. The trigger for SR release is voltage. Voltage Activated Calcium Release. (VACR) 2. The T tubule membrane has a voltage sensor (DHP receptor) 3. The ryanodine receptor is the SR Ca release channel 4. Ca release is proportional to membrane voltage Cardiac Muscle 1. The trigger for SR release is calcium. Calcium Activated Calcium Release. (CACR) 2. The T tubule membrane has a Ca channel (DHP receptor) 3. The ryanodine receptor is the SR Ca release channel. 4. The ryanodine receptor is Ca gated and Ca release is proportional to Ca entry.