Generation & Conduction of Action Potentials

Csilla Egri, KIN 306 Spring 2012

Speed 2 had action potential…but failed to deliver

Outline2

Synaptic transmission Gap junctions Chemical synapses

Neurotransmitters Neurotransmitter receptors

Synaptic integration Signal propagation

Electrotonic conduction Action potentials

Nerve conduction disorders

Synaptic transmission - introduction

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http://kin450-neurophysiology.wikispaces.com/Synaptic+Transmission

Chemical synapseElectrical synapse

Electrical Synapses: Gap Junctions

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Present in nervous system between glial cells and certain neurons in regions such as the cerebellum, spinal cord, thalamus, hippocampus, olfactoray bulb, retina, and striatum

Information can be bidirectional and results in no synaptic delay in communication and synchronized neuronal activity

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Neurotransmitters: overview of major classes

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Class/chemical Some Facts (B&L pg. 95-100)Acetylcholine (ACh)

Found in neuromuscular junctions and autonomic nervous system

Amines Can function as neurohormones/hormones.Norepinephrine (NE) Found diffusely thru CNS and also in sympathetic neurons.

Dopamine (DA) Associated with reward driven behaviour.Serotonin (5-HT) Thought to contribute to feelings of well-being and happiness.Amino Acids

Glutamate Major excitatory neurotransmitter of the CNS.GABA Major inhibitory neurotransmitter of the CNSGlycine Inhibitory in spinal cord, brainstem, retina and cerebellum.Purines

ATP Co-released from vesicles in almost all synaptic transmission.Peptides More than 100 types of active neuropeptides.Substance P Involved in pain transmission and effects smooth muscle cellsGases Not packaged into vesicles and not released via exocytosis; diffuses thru synaptic cleft.

Nitric Oxide (NO) Can also function as signal transduction molecule.

Neurotransmitter Receptors7

the response(s) elicited by a neurotransmitter is determined by receptor to which it binds

Two general families: Ionotropic receptors (ligand gated ion

channels) Directly linked to ion channels Activation results in post synaptic events that are

rapid in onset and decay Metabotropic receptors (G-protein coupled

receptors) Activation results in modification of enzyme or

membrane proteins Post synaptic events have slower onset and longer

duration

Ionotropic Receptors8

Two functional domains extracellular site binds

neurotransmitters membrane-spanning

domain forms ion channel

Examples: ionotropic glutamate

receptors ionotropic GABA

receptors nicotinic Ach receptor B&L Figure 6-12

Metabotropic Receptors9

Two functional domains: extracellular domain binds

neurotransmitters intracellular domain binds to

G-proteins G proteins couples

neurotransmitter binding to modulation of intracellular or membrane proteins

Examples: metabotropic glutamate

receptors muscarinic acetylcholine

(Ach) receptors adrenergic receptors B&L Figure 6-12

Postsynaptic Potentials (PSP)10

Binding of neurotransmitters to the post synaptic membrane can either be:

Excitatory (produces EPSP) Depolarizes membrane potential

Inhibitory (produces IPSP) Hyperpolarizes membrane potential

Both types of PSPs are graded potentials (as opposed to action potentials)

EPSPs and IPSPs11

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EPSP IPSP

Post Synaptic Integration12

Most synaptic input occurs in dendrites or the cell body Amplitude of many graded PSPs from synaptic

inputs can sum, potentially triggering an action potential at the axon hillock = postsynaptic integration

Spatial Summation summation of simultaneous inputs at different

sites Temporal Summation

summation of consecutive inputs at same site

Spatial and Temporal Summation

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B&B Figure 11-11

Signal Propagation: Electrotonic conduction

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Amplitude of electrotonic signals decrease exponentially with membrane distance. This is due to: membrane resistance (rm)

Current leak across the membrane (membranes are poor insulators)

axoplasmic/axial resistance (ra) Impedance of current flow thru the cytoplasm

(cytoplasm is a poor conductor)

Electrotonic conduction: length constant

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Signal decay is determined by the length constant (λ)

Distance over which signal decays to 37% of original size

Does a high ra increase ordecrease the length

constant?

How would you increase rm?

am rr /=λ

B&L Figure 5-3

Signal Propagation: Action Potentials (Review)

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Transient, regenerative, constant amplitude signal that propagates long distances

Requires a high density of voltage-gated ion channels

Initiated when excitatory graded potentials arrive at axon hillock if Vm is above a threshold voltage (-55mV)

Different ionic currents determine each phase of AP

B&BFigure 7-1

Signal Propagation: Action Potentials (Review)

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Threshold, amplitude, time course and duration depend on:

Gating properties and permeability's of ion channels (NaV, KV, CaV, ClV)

Intra/extracellular ionic concentration gradients

Membrane properties such as resistance, capacitance and cell geometry

Bean, J. The action potential in mammalian central neurons. Nature Reviews. 2007

Action Potentials: Ionic contributions

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Membrane depolarization increases open probability of NaV channels Na conductance (gNa) increases and moves membrane potential towards ENa

NaV channels inactivate 1-2 ms after opening, reducing gNa

Slower to open voltage gated K+ channels activate & rapidly repolarize membrane

Brief undershoot, then Vm returns to resting value after K+ channels close

B&B Figure 7-4

Action Potentials: Ionic contributions

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Absolute refractory period

Due to NaV channel inactivation

Prevents APs from travelling backwards along axon

Sets maximum AP frequency

Relative refractory period

Due to high gK Also involved in

determining AP frequency

B&B Figure 7-3

So now that you know about ionic contributions, what could cause a plateau phase?

Action Potential Propagation20

AP propogation also governed by membrane and cytoplasm resistance Larger diameter neurons conduct action potentials faster (decrease

ra) But there is a limit on mammalian neuron diameter

Mammals achieve increased conduction speed via myelination (increase rm)

B&B Figure 11-9

High density of ion channels

Little to no ion channels. Signal propagates passively (electrotonic conduction)

Signal regenerates and jumps from node to node

Nerve Conduction Disorders21

Demyelination Demyelinated axons

conduct action potentials slowly, unreliably, or not at all

Signal block leads to more serious consequences than decreased conduction velocity

B&B Figure 11-9

Nerve Conduction Disorders22

Demyelination A signal from one

demyelinated axon can excite an adjacent demyelinated axon (crosstalk), causing action potentials to be conducted in both directions in the adjacent axon.

B&B Figure 11-9

Nerve Conduction Disorders23

Multiple Sclerosis (MS) Most common CNS demyelination disorder Autoimmune disease that targets myelin directly or the oligodendrocyte cells Symptoms vary depending on location of demyelination,

but can include visual impairments, numbness or tingling, loss of balance, weakness, bowel and bladder problems, hearing loss

Remission and relapse common CNS inflammation, stress, or heat can exacerbate

symptoms

WebCT readings: Multiple Sclerosis

ObjectivesAfter this lecture you should be able to: Describe the process of synaptic transmission, beginning

from an action potential arriving at the pre synaptic membrane

Distinguish between ionotropic and metabotropic receptors Relate physical properties of neurons to speed of signal

conduction and signal decay List the differences between graded potentials and action

potentials Describe the phases and ionic components of a neuronal

action potential Understand how action potentials are propagated and how

demyelination affects signal propagation Relate these consequences to the CNS demyelination disorder; MS

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1. What role would the length constant play in spatial summation of post synaptic potentials?

2. How is the intensity/strength of a stimulus coded for in a graded potential (electrotonic conduction) vs. an action potential?

3. How does myelination of an axon change the membrane resistance and membrane capacitance? How does this affect conduction speed?

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