pineda. membrane electrophysiology and synapse physiology

8/12/2019 PINEDA. Membrane Electrophysiology and Synapse Physiology

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SAN BEDA COLLEGE OF MEDICINE

MEMBRANE ELECTROPHYSIOLOGY NERVE AND SYNAPTIC PHYSIOLOGY BY MICHAEL PINEDA, MD

SAN BEDA COLLEGE OF MEDICINE Page 1 of 6MEMBRANE AND SYNAPSE PHYSIOLOGY BY MICHAEL PINEDA, MD

MEMBRANE ELECTROPHYSIOLOGY/ NERVE AND SYNAPTICPHYSIOLOGY

By Michael Pineda, MD

[email protected]

09989765120

MEMBRANE ELECTROPHYSIOLOGY

EDUCATIONAL OBJECTIVESAt 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 inpermeabilities of sodium, potassium and

chloride and large proteins on the RMP.

Explain the Gibbs-Donnan Equilibrium. Explain the Nernst Equation.

2Describe how local potential are produced. Enumerate the characteristics of a localpotential 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 nerveas recorded internally.

Describe the sequence of changes inmembrane permeability and the ionic

movements.

Give the role of the sodium-potassium-ATPasepump.

Differentiate depolarization or firing level(threshold potential), repolarization and

hyperpolarization.

Differentiate absolute from relative refra

ctory

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 eachpart.

Classify the nerve fibers and give theirdistinctive characteristics.

5.Define excitability and stimulus. Give the characteristics of an effective

stimulus.

Draw the strength-duration curve. Give itsclinical 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 distinguishtransmission across synapse from conduction

along a peripheral nerve

RESTING MEMBRANE POTENTIAL

Combination of the following results in the RestingMembrane 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 potentialenergy. Like a stretched rubber band!

PROPERTIES OF RESTING POTENTIAL

Potassium and sodium ion channels allow leakage ofthese 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 Forcesare Equally Strong

The NERST EQUATION determines the equilibrium ofthese two forces

NERNST EQUATION

diffusion potential level across a membrane that exactlyopposes the net diffusion of a particular ion

determined by the ratioof the concentrations of thatspecific ion on the two sides of the membrane

greater this ratio, the greater the tendency for the ion todiffuse in one direction, and therefore the greater the
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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 ofsolutions 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, membranepotential moves closer to the equilibrium potential for

that ion

If permeability to a certain ion decreases, membranepotential 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 besummated.

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 postsynapticcell, moving it away from threshold and

farther from firing

caused by opening Cl-channelsSUMMATION

process of adding up postsynaptic potentials andresponding to their net effect

Temporal Summation: repeated stimuli withina brief time have a cumulative effect.

Spatial Summation: several inputs fromdifferent regions of the membrane combine

their effects in a neuron

Figure 5. Summation

ACTION POTENTIAL

a rapid, all-or-none change in the membrane potentialfollowed by a return to the resting membrane potential.

is a property of excitable cells (i.e., nerve, muscle) thatconsists of a rapid depolarization, or upstroke, followed

by repolarization of the membrane potential

Action potentials have stereotypical size and shape, arepropagating, and are all-or-none.

Neurons communicate by producing electrical impulsescalled Action Potentials

Voltage-gated Na Channels: Open when impinged withdepolarization FURTHER depolarizing the membrane.

Firing Threshold Level: -55 mV: Depolarization risessharply to produce an action potential.


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The Action Potential is a depolarization of up to 100mV

It follows the All-or-None principle Neurons generate action potentials by opening Sodium

Channels

As the Action Potential passes, repolarization occursrapidly

Opening of the K channels, tend to hyperpolarize theneuron

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 withdecreased threshold.

ACCOMODATION

occurs when the cell membrane is held at a depolarizedlevel such that the threshold potential is passed without

firing an action potential.

occurs because depolarization closes inactivation gateson the Na+channels.

PROPAGATING ACTION POTENTIAL

- Action potential is regenerated ineach node of Ranvier

- SALTATORY condution

NERVE AND SYNAPSE PHYSIOLOGY

ORGANIZATION OF THE NERVOUS SYSTEM

Enables the body to react to continuous changes in itsexternal and internal environments.

Controls and integrates the various activities of thebody, such as circulation and respiration.

Organization of the Nervous System

Neurons are the structural and functional units ofthe nervous system

Neurons are specialized for rapid communicationSpecial Neuron Features

Dendrites Dendritic spines

Cell body Axons

Myelin sheath Nodes of Ranvier Pre-synaptic terminal/terminal


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Structure of Neurons

NERVE CLASSIFICATION

- Depends on myelination- Nerve fiber diameter

SYNAPSE

Signals are transferred from one cell toanother via a synapse

Electrical or chemicalElectrical 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 intermediariescalled 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 fuseat active zones

SNARE proteins v-SNARES t-SNARES

Zipper-like interaction between synpatobrevin,syntaxin and SNAP-25


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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)

PurinesACETYLCHOLINE

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 asincreasing the level of wakefulness

may be excitatory or inhibitoryaction 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 asincreasing the level of wakefulness

may be excitatory or inhibitoryaction terminated by reuptake (NET) and metabolism

(monoamine oxidase, catechol-O-methyltransferase

SOURCES:

1. Guyton & Hall Textbook of Medical Physiology 12thEdition by Hall, John &, Guyton, Arthur C. , , Published in

Philadelphia, Pensylvania: Saunders/Elsevier, 2011

2. Berne & Levy Physiology 6thEdition bby Berne, RobertM., 1918-2001., Koeppen, Bruce M., Published:

Philadelphia : Mosby/Elsevier, 2008

3. Ganong Review of Medical Physiology, 23rdEdition, byBarrett, Kim , Barrett, Kim E., Barman, Susan, Boitano,

Scott, Brooks, Heddwen, Published: New York :

McGraw-Hill Medical, 2010

4. BRS Physiology 5thEdition by Linda Constanzo, 2011,Published: Lippincott and Williams & Wilkins


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5. Kaplan Medical Step 1 Lecture Notes (Physiology) 20106. Medical Physiology: Big Picture by By (author) Jonathan

Kibble, Colby Halsey, Published: Lange

7. Harpers Illustrated Biochemistry 27thEdition byMurray, Robert K. by Lange

8. Basic and Clinical Pharmacology 11thEdition by byKatzung, Bertram G. , Published: New York : McGraw-

Hill Medical, 2009

9. SBCM Physiology Lectures10. Various Internet Websites

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