SAN BEDA COLLEGE OF MEDICINE

MEMBRANE ELECTROPHYSIOLOGY NERVE AND SYNAPTIC PHYSIOLOGY BY MICHAEL PINEDA, MD

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MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD

MEMBRANE ELECTROPHYSIOLOGY/ NERVE AND SYNAPTIC
PHYSIOLOGY
By Michael Pineda, MD
mikepinedamd@gmail.com
09989765120

MEMBRANE ELECTROPHYSIOLOGY

EDUCATIONAL OBJECTIVES
At the end of the 4-hour lecture, the future Bedan Doctor must be
able to:

1. Define equilibrium potential.
Explain the basis for the Resting Membrane
Potential (RMP).
Give the effects of the differences in
permeabilities of sodium, potassium and
chloride and large proteins on the RMP.
Explain the Gibbs-Donnan Equilibrium.
Explain the Nernst Equation.

2 Describe how local potential are produced.
Enumerate the characteristics of a local
potential
Name and differentiate types of local
potentials
3. Explain the events that underlie the initiation and propagation
of an action potential.
Draw and label the action potential of a nerve
as recorded internally.
Describe the sequence of changes in
membrane permeability and the ionic
movements.
Give the role of the sodium-potassium-ATPase
pump.
Differentiate depolarization or firing level
(threshold potential), repolarization and
hyperpolarization.
Differentiate absolute from relative refractory
period
4. Discuss the structural basis of nerve function.
Describe the general organization of the
nervous system.
Draw a neuron and give the function of each
part.
Classify the nerve fibers and give their
distinctive characteristics.
5. Define excitability and stimulus.
Give the characteristics of an effective
stimulus.
Draw the strength-duration curve. Give its
clinical significance.

6. Discuss the All or None Law of nerve fibers.
Give the structural characteristics of a synapse
and their importance.
Enumerate some features which distinguish
transmission across synapse from conduction
along a peripheral nerve


















RESTING MEMBRANE POTENTIAL
Combination of the following results in the Resting
Membrane Potential:
Potassium diffusion
Sodium diffusion
Na
+
, K
+
- ATPase
____________ is the major determinant of the Resting
Membrane Potential




Figure 1. Resting Membrane Potential

WHY A RESTING POTENTIAL?
Why not have the Resting Membrane Potential to 0 mv?
Evolutionary Advantage: The resting potential prepares
the neurons to respond rapidly to a stimulus.
The Resting Membrane Potential is a source of potential
energy. Like a stretched rubber band!

PROPERTIES OF RESTING POTENTIAL
Potassium and sodium ion channels allow leakage of
these ions across the cell membranes
In the normal nerve fiber, the permeability of the
membrane to potassium is about 100 times as great as
to sodium

Figure 2. Intracellular and Extracellular Ion Compositions

FORCES OF THE RESTING POTENTIAL
Passive Forces acting on the Membrane
Chemical Force: Moves Na+ inward and K+
outward (Passive Diffusion)
Electrical Force: Moves Na+ and K+ inward
(Coloumbs Law)
Equilibrium Potential: Chemical and Electrical Forces
are Equally Strong
The NERST EQUATION determines the equilibrium of
these two forces

NERNST EQUATION
diffusion potential level across a membrane that exactly
opposes the net diffusion of a particular ion
determined by the ratio of the concentrations of that
specific ion on the two sides of the membrane
greater this ratio, the greater the tendency for the ion to
diffuse in one direction, and therefore the greater the

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MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD
Nernst potential required to prevent additional net
diffusion

Figure 3. NERNST EQUATION


Table 1. Concentration of Ions and Equilibrium Potential

Gibbs-Donnan Equlibrium
The GibbsDonnan equilibrium is a phenomenon of
solutions that contributes to the formation of an
electrical potential across a cell membrane
Figure 4. Gibbs-Donnan Equilibrium

NOTES:
Resting Membrane Potential: -70 mV
Membrane Potential is affected by the relative
permeability of each ion
If a permeability to a certain ion increases, membrane
potential moves closer to the equilibrium potential for
that ion
If permeability to a certain ion decreases, membrane
potential moves away from the equilibrium potential of
that ion

Goldman-Hodgkin-Katz Equation



Na-K ATPase pump
Maintains the Resting Membrane Potential
Pumps 3 Na+ out in exchange for 2 K+
Uses ATP (Active Transport)



GRADED RESPONSES
Membrane potentials that vary in magnitude and can be
summated.
Examples:
Receptor Potentials
Synaptic Potentials

POSTSYNAPTIC POTENTIALS
EXCITATORY POSTSYNAPTIC POTENTIALS (EPSP)
inputs that depolarize the postsynaptic cell,
bringing it closer to threshold and closer to
firing an action potential
caused by opening of Na
+
and K
+
channels
INHIBITORY POSTSYNAPTIC POTENTIALS (IPSP)
inputs that hyperpolarize the postsynaptic
cell, moving it away from threshold and
farther from firing
caused by opening Cl
-
channels
SUMMATION
process of adding up postsynaptic potentials and
responding to their net effect
Temporal Summation: repeated stimuli within
a brief time have a cumulative effect.
Spatial Summation: several inputs from
different regions of the membrane combine
their effects in a neuron

Figure 5. Summation

ACTION POTENTIAL
a rapid, all-or-none change in the membrane potential
followed by a return to the resting membrane potential.
is a property of excitable cells (i.e., nerve, muscle) that
consists of a rapid depolarization, or upstroke, followed
by repolarization of the membrane potential
Action potentials have stereotypical size and shape, are
propagating, and are all-or-none.
Neurons communicate by producing electrical impulses
called Action Potentials
Voltage-gated Na Channels: Open when impinged with
depolarization FURTHER depolarizing the membrane.
Firing Threshold Level: -55 mV: Depolarization rises
sharply to produce an action potential.

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MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD
The Action Potential is a depolarization of up to 100
mV
It follows the All-or-None principle
Neurons generate action potentials by opening Sodium
Channels
As the Action Potential passes, repolarization occurs
rapidly
Opening of the K channels, tend to hyperpolarize the
neuron


Figure 6. Action Potential

Molecular Events in Action Potential



Refractory Period
Refractory Period: period of decreased excitability
Absolute: an Action Potential cannot be
generated
Relative: another Action Potential with
decreased threshold.

ACCOMODATION
occurs when the cell membrane is held at a depolarized
level such that the threshold potential is passed without
firing an action potential.
occurs because depolarization closes inactivation gates
on the Na
+
channels.



PROPAGATING ACTION POTENTIAL

- Action potential is regenerated in
each node of Ranvier
- SALTATORY condution




NERVE AND SYNAPSE PHYSIOLOGY

ORGANIZATION OF THE NERVOUS SYSTEM
Enables the body to react to continuous changes in its
external and internal environments.
Controls and integrates the various activities of the
body, such as circulation and respiration.

Organization of the Nervous System

Neurons are the structural and functional units of
the nervous system
Neurons are specialized for rapid communication

Special Neuron Features
Dendrites
Dendritic spines
Cell body
Axons
Myelin sheath
Nodes of Ranvier
Pre-synaptic terminal/terminal



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MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD

Structure of Neurons

NERVE CLASSIFICATION

- Depends on myelination
- Nerve fiber diameter

SYNAPSE
Signals are transferred from one cell to
another via a synapse
Electrical or chemical

Electrical Synapses
Gap junctions
low-resistance pathway between cells that
allows current to flow directly from one cell to
another
Direct communication between the cytoplasm



Chemical Synapse
Cell membranes are separated (20 um)
Communication occur via intermediaries
called neurotransmitters
Unidirectional
Presynaptic
Postsynaptic

Chemical Synapse

TYPES OF SYNAPSE
axodendritic or axosomatic synapses
Axoaxonic
Dendrodendritic
dendrosomatic

NEUROTRANSMITTER RELEASE: SUMMARY


RELEASE OF NEUROTRANSMITTER
Small vesicles contaning nonpeptide NTs can only fuse
at active zones
SNARE proteins
v-SNARES
t-SNARES
Zipper-like interaction between synpatobrevin,
syntaxin and SNAP-25





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MEMBRANE ELECTROPHYSIOLOGY NERVE AND SYNAPTIC PHYSIOLOGY BY MICHAEL PINEDA, MD
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MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD
NEUROTRANSMITTERS
mediate chemical signaling between neurons
Criteria to be a Neurotransmitter:
there should be specific receptors for it
the cell must be able to synthesize the
substance
released on depolarization of the terminal
there should be specific receptors
Three major categories: small-molecule transmitters,
peptides, and gaseous transmitters

TYPES OF NEUROTRANSMITTERS
Amino acids
glutamate, GABA, glycine, aspartate,
Neuropeptides
Endorphin, Substance P
Acetylcholine
Gases
Nitric Oxide
Monoamines
Indoleamine
Serotonin
Cathecholamine
Norepinehprine,
Epinephrine
Dopamine
Purines
ATP, adenosine

SYNTHESIS OF NEUROTRANSMITTERS



AXONAL TRANSPORT


SMALL MOLECULES NT
Acetylcholine
Amino Acids (glutamate, GABA, glycine)
Biogenic Amines (dopamine, norepinephrine,
epinephrine, serotonin, histamine)
Purines

ACETYLCHOLINE
PNS: NMJ, sympathetic and parasympathetic ganglia
CNS: Brainstem, septal nuclei and nucleus basalis
synthesized from acetyl coenzyme A and choline by
choline acetyltransferase
may be excitatory or inhibitory
action terminated by metabolism (enzymatic
degradation) by acetylcholinesterase
Degraded by Acetylcholinesterase
secreted by neurons in many areas:
large pyramidal cells in motor cortex
basal ganglia (nucleus basalis of Meynert)
skeletal muscles
all preganglionic neurons of ANS
postganglionic neurons of parasympathetic NS
some postganglionic neurons of sympathetic
NS


EPINEPHRINE AND NOREPINEPHRINE
secreted by many neurons:
brain stem
hypothalamus
locus ceruleus in the pons
postganglionic neurons of sympathetic
nervous system
control overall activity and mood of the mind, such as
increasing the level of wakefulness
may be excitatory or inhibitory
action terminated by reuptake (NET) and metabolism
(monoamine oxidase, catechol-O-methyltransferase

SUMMARY OF NEUROTRANSMITTERS
secreted by many neurons:
brain stem
hypothalamus
locus ceruleus in the pons
postganglionic neurons of sympathetic
nervous system
control overall activity and mood of the mind, such as
increasing the level of wakefulness
may be excitatory or inhibitory
action terminated by reuptake (NET) and metabolism
(monoamine oxidase, catechol-O-methyltransferase


SOURCES:

1. Guyton & Hall Textbook of Medical Physiology 12
th

Edition by Hall, John &, Guyton, Arthur C. , , Published in
Philadelphia, Pensylvania: Saunders/Elsevier, 2011
2. Berne & Levy Physiology 6
th
Edition bby Berne, Robert
M., 1918-2001., Koeppen, Bruce M., Published:
Philadelphia : Mosby/Elsevier, 2008
3. Ganong Review of Medical Physiology, 23
rd
Edition, by
Barrett, Kim , Barrett, Kim E., Barman, Susan, Boitano,
Scott, Brooks, Heddwen, Published: New York :
McGraw-Hill Medical, 2010
4. BRS Physiology 5
th
Edition by Linda Constanzo, 2011,
Published: Lippincott and Williams & Wilkins

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MEMBRANE ELECTROPHYSIOLOGY NERVE AND SYNAPTIC PHYSIOLOGY BY MICHAEL PINEDA, MD
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MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD
5. Kaplan Medical Step 1 Lecture Notes (Physiology) 2010
6. Medical Physiology: Big Picture by By (author) Jonathan
Kibble, Colby Halsey, Published: Lange
7. Harpers Illustrated Biochemistry 27
th
Edition by
Murray, Robert K. by Lange
8. Basic and Clinical Pharmacology 11
th
Edition by by
Katzung, Bertram G. , Published: New York : McGraw-
Hill Medical, 2009
9. SBCM Physiology Lectures
10. Various Internet Websites