ANSWER THE ESSAYS AND THE BULLET (-) QUESTIONS

APLECTURE19ElectrophysiologyofNeurons.ppt

Home >Biology homework help >Anatomy homework help >ANSWER THE ESSAYS AND THE BULLET (-) QUESTIONS

Electrophysiology of Neurons

-cellular mechanisms for producing
electrical potentials & currents

-basis for neural communication &
muscle contraction

electrical potential– a concentration difference of charged

particles between two points

electrical current – a flow of charged particles from one

point to another

cells- movement of ions (Na+ K+) across plasma membrane

living cells are polarized

resting membrane potential (RMP) – charge difference

across the plasma membrane

-70 mV in a resting, unstimulated neuron
negative value => Neg > inside than outside of cell

Electrical Potentials and Currents

RMP exists because of unequal electrolyte distribution

across the plasma membrane

RMP arises from all of the following:
ions diffuse down their concentration gradient through the membrane

plasma membrane is selectively permeable and allows some ions to pass easier than others

electrical attraction of cations and anions to each other

Resting Membrane Potential

Creation of Resting Membrane Potential

potassium ions (K+) have the greatest influence on RMP
K+ -most permeable to plasma membrane
K+ -~40 times concentrated inside the cell

Cytoplasmic anions (ATP, RNA)
not permeable
due to size or charge

Sodium ions (Na+) lesser influence on RMP
some leaks and diffuses into the cell down its concentration gradient
Na+ -~12 times as concentrated outside the cell
resting membrane is much less permeable to Na+ than K+

Na+/K+ pumps out 3 Na+ for every 2 K+ it brings in
70% of energy requirement of nervous system

Na+ concentrated outside of cell
K+ concentrated inside cell

ECF

ICF

Na+

channel

K+

channel

Na+ 145 mEq/L

K+ 4 mEq/L

Na+ 12 mEq/L

K+ 150 mEq/L

Large anions

that cannot

escape cell

Ionic Basis of Resting Membrane Potential

12-*

Local Potentials- membrane potential disturbance
upon neuron stimulation

neuron response
begins at the dendrite,
spreads through the soma,
travels down the axon,
and ends at the synaptic knobs

Neuron stimulation by chemicals, light, heat or mechanical disturbance
Na+ channels open & Na+ flows in to the cell
Na+ inflow reduces internal negative charge
voltage decreases across the membrane

(depolarization - membrane voltage shifts to a less negative value)

Na+ diffuses for short distance on the inside of the plasma membrane producing a current that travels towards the cell’s trigger zone – this short-range change in voltage is called a local potential

local potentials vs action potentials

graded - magnitude varies with stimulus strength
stronger stimuli open more Na+ gates

decremental – decrease from stimulation point
voltage shift Na+ inflow diminishes rapidly w/ distance

reversible - stimulation ceases, K+ diffusion out of cell

returning cell to RMP

excitatory or inhibitory -

Neuron Excitation by a Chemical Stimulus

Dendrites

Soma

Axon

Current

Na+

ECF

ICF

Trigger

zone

Ligand

Plasma

membrane

of dendrite

Receptor

Action Potentials

larger change by voltage-regulated ion gates in plasma membrane

requires high enough density of voltage-regulated gates

soma (50 -75 gates per m2 ) - cannot generate an action potential

trigger zone (350 – 500 gates per m2 ) – where action potential is

generated

rapid up-&-down shift in membrane voltage

sodium ions arrive at the axon hillock

depolarize the membrane at that point

threshold – critical voltage to which local potentials must rise to open the voltage-regulated gates
-55mV

Na+ channels open in trigger zone (positive feedback)
creating rapid rise in membrane voltage – spike

At 0 mV, Na+ gates are inactivated
when all closed, the voltage peaks at +35 mV
membrane now positive on inside and negative on outside
polarity reversed from RMP - depolarization

At peak voltage, the slow K+ gates fully open
K+ outflow repolarizes the membrane

K+ gates stay open longer than the Na+ gates
slightly more K+ leaves the cell than Na+ entering
membrane voltage drops 1-2mV than original RMP (hyperpolarization)

Na+ and K+ switch places across membrane during action potential

Action Potentials- threshold reached, neuron
‘fires’ producing action potential

Action Potentials

only a thin layer of cytoplasm next to the cell membrane is affected

often called a spike

action potential vs. local potential
all-or-none law
if threshold reached, neuron fires at its maximum voltage
if threshold is not reached it does not fire
nondecremental - do not get

weaker with distance

irreversible - once started,

completes

Time

–70

Depolarization

Repolarization

Hyperpolarization

Threshold

+35

–55

Local

potential

Resting membrane

potential

Action

potential

Sodium and Potassium Gates

–70

Repolarization complete

Na+

Na+ gates closed,

K+ gates closing

K+

Na+

gate

K+

gate

–70

Na+ and K+ gates closed

Resting membrane

potential

–70

Depolarization begins

Na+ gates open, Na+

enters cell, K+ gates

beginning to open

–70

Na+ gates closed, K+ gates

fully open, K+ leaves cell

Depolarization ends,

repolarization begins

The Refractory Period- period of resistance
to stimulation

during an action potential & for few milliseconds after

refractory period occurs only at a small patch of the neuron’s membrane at one time

other parts of the neuron can be stimulated while the small part is in refractory period

Threshold

Time

+35

–55

–70

Absolute

refractory

period

Relative

refractory

period

Resting membrane

potential

Saltatory Conduction in Myelinated Fibers

voltage-gated channels needed for APs
<25 per m2 -myelin-covered regions (internodes)
~12,000 per m2 -nodes of Ranvier
fast Na+ diffusion occurs between nodes
saltatory conduction – the nerve signal seems to jump from node to node

(a)

Na+ inflow at node

generates action potential

(slow but nondecremental)

Na+ diffuses along inside

of axolemma to next node

(fast but decremental)

Excitation of voltage-

regulated gates will

generate next action

potential here

Synapses

a nerve signal stops when it reaches the end of the axon
triggers the release of a neurotransmitter
continues nerve signal in neuron across synapse

synapse between two neurons
1st- presynaptic neuron releases neurotransmitter
2nd- postsynaptic neuron responds to neurotransmitter

presynaptic neuron may synapse with a dendrite, soma, or axon of postsynaptic neuron

neuron can have an enormous number of synapses (~100,000, cerebellum)

Structure of a Chemical Synapse

presynaptic neurons have synaptic vesicles with neurotransmitter
postsynaptic have receptors and ligand-regulated ion channels

Axon of presynaptic neuron

Postsynaptic neuron

Mitochondria

Synaptic cleft

Synaptic knob

Microtubules

of cytoskeleton

Synaptic vesicles

containing neurotransmitter

Neurotransmitter

receptor

Neurotransmitter

release

Neurotransmitters

>100 neurotransmitters identified

four major chemical categories
acetylcholine
amino acid neurotransmitters (glutamate, -aminobutyric acid (GABA))
monoamines (epinephrine, seratonin, dopamine
neuropeptides

Categories of Neurotransmitters

Acetylcholine

Monoamines

CH3

N+

CH2

CH3

Amino acids

CH2

NH2

GAB

CH2

NH2

Glycine

CH2

Aspartic acid

NH2

CH2

Glutamic acid

NH2

Catecholamines

CH2

Epinephrine

CH2

NH2

Norepinephrine

CH2

NH2

Dopamine

CH2

NH2

Serotonin

CH2

NH2

Histamine

Neuropeptides

Enkephalin

Cholecystokinin

ß-endorphin

SO4

Met

Phe

Gly

Tyr

Arg

Lys

Pro

Glu

Phe

Gly

Leu

Met

Glu

Asp

Tyr

Met

Gly

Trp

Met

Asp

Phe

Substance P

Tyr

Gly

Phe

Met

Thr

Ser

Glu

Lys

Ser

Glu

Thr

Pro

Leu

Val

Thr

Leu

Phe

Lys

Asn

Ala

IIe

Lys

Asn

Ala

Tyr

Lys

Gly

Glu

H3C

Neuropeptides

chains of 2-40 amino acids

beta-endorphin and substance P

act at lower concentrations than other neurotransmitters

longer lasting effects

stored in axon terminal as larger secretory granules (called dense-core vesicles)

Neuropeptides

Enkephalin

Cholecystokinin

ß-endorphin

SO4

Met

Phe

Gly

Tyr

Arg

Lys

Pro

Glu

Phe

Gly

Leu

Met

Glu

Asp

Tyr

Met

Gly

Trp

Met

Asp

Phe

Substance P

Tyr

Gly

Phe

Met

Thr

Ser

Glu

Lys

Ser

Glu

Thr

Pro

Leu

Val

Thr

Leu

Phe

Lys

Asn

Ala

IIe

Lys

Asn

Ala

Tyr

Lys

Gly

Glu

Neurotransmitter Function at Synapse

synthesized by the presynaptic neuron

released in response to stimulation

specific receptors on the postsynaptic cell

alter the physiology of that cell

Neurotransmitters Effects

neurotransmitter does not have the same effect everywhere in the body

multiple receptor types exist for a particular neurotransmitter
14 receptor types for serotonin

receptor governs effect the neurotransmitter has on target cell

Synaptic Transmission

neurotransmitters are diverse in their action
excitatory or inhibitory
effect dependent on postsynaptic receptor type
open ligand-regulated ion gates
act through second-messenger systems

three kinds of synapses with different modes of action
excitatory cholinergic synapse
inhibitory GABA-ergic synapse
excitatory adrenergic synapse

synaptic delay – time nerve signal arrival at presynaptic axon terminal to beginning of postsynaptic action potential (0.5 msec)

Excitatory Cholinergic Synapse

Presynaptic neuron

Postsynaptic neuron

Presynaptic neuron

Ca2+

Na+

ACh

K+

–

cholinergic synapse – acetylcholine (ACh)

ACh excites some postsynaptic cells

skeletal muscle inhibits others

Inhibitory GABA-ergic Synapse

GABA-ergic synapse employs -aminobutyric acid as its neurotransmitter

nerve signal triggers release of GABA into synaptic cleft

GABA receptors are chloride channels

Cl- enters cell and makes the inside more negative than the resting membrane potential

postsynaptic neuron is inhibited, and less likely to fire

Excitatory Adrenergic Synapse

cAMP

Enzyme activation

Genetic transcription

Enzyme synthesis

Na+

Adenylate cyclase

G protein

–

Postsynaptic neuron

Presynaptic neuron

Norepinephrine

Neurotransmitter

receptor

Ligand-

regulated

gates

opened

Multiple

possible

effects

Metabolic

changes

ATP

Postsynaptic

potential

adrenergic synapse-

norepinephrine (NE)

aka noradrenaline

mechanisms to stop postsynaptic neuron firing indefinitely
neurotransmitter binds receptor (transiently, 1msec)

stop adding neurotransmitter and get rid of that which is already there
stop signals in the presynaptic nerve fiber
getting rid of neurotransmitter by:
diffusion
reuptake
degradation in the synaptic cleft
enzyme acetylcholinesterase in synaptic cleft degrades ACh

Cessation of the Signal

12-*

Postsynaptic Potentials - EPSP

neural integration is based on the postsynaptic potentials produced by neurotransmitters

typical neuron has a resting membrane potential of -70 mV and threshold of about -55 mV

excitatory postsynaptic potentials (EPSP)
any voltage change in the direction of threshold that makes a neuron more likely to fire
usually results from Na+ flowing into the cell cancelling some of the negative charge on the inside of the membrane

glutamate and aspartate are excitatory brain neurotransmitters that produce EPSPs

Postsynaptic Potentials - IPSP

inhibitory postsynaptic potentials (IPSP)
voltage change from threshold, renders neuron less likely to fire
hyperpolarizes the postsynaptic cell
open ligand-regulated chloride gates
causing inflow of Cl- making the cytosol more negative

glycine and GABA produce IPSPs and are inhibitory

acetylcholine (ACh) and norepinephrine are excitatory to some cells and inhibitory to others
depending on the type of receptors on the target cell
ACh excites skeletal muscle, but inhibits cardiac muscle

one neuron can receive input from thousands of other neurons

some incoming nerve fibers produce EPSPs & others produce IPSPs

neuron’s response- the net input, excitatory or inhibitory

summation –add postsynaptic potentials & respond to net effect
occurs in the trigger zone

Summation, Facilitation, and Inhibition

Summation of EPSPs

does this represent spatial or temporal summation?

Threshold

EPSPs

Stimuli

+40

+20

–20

–40

–60

–80

Action potential

Time

Resting

membrane

potential

100,000 deaths/year; 11% of population over 65; 47% by age 85

memory loss for recent events, moody, combative, progressive

show deficiencies of acetylcholine and nerve growth factor

diagnosis confirmed at autopsy
atrophy of gyri (folds) in cerebral cortex
beta-amyloid protein from breakdown product of plasma membranes

genetics implicated

treatment - halt beta-amyloid production; NGF, cholinesterase inhibitors

Alzheimer Disease

Alzheimer Disease Effects

(a)

Shrunken

gyri

Wide sulci

Custom Medical Stock Photo, Inc.

(b)

Senile plaque

Neurons with

neurofibrillary

tangles

Parkinson Disease

progressive loss of motor function in 50-60’s w/ no recovery
degeneration of dopamine-releasing neurons
dopamine normally prevents excessive activity in motor centers
involuntary muscle contractions

treatment - drugs and physical therapy
dopamine precursor (L-dopa) crosses brain barrier – bad side effects on heart & liver
MAO inhibitor slows neural degeneration
surgical technique to relieve tremors