Nerve Action potential L 21

Learning objectives Genesis of nerve action potential Potential changes, phases of AP Ionic basis Role of voltage gated channels Differences between AP & electrotonic potentials Properties of Nerve action potential Propagation of action potentials in nerve fibers All or none law Refractory period and significance

NERVE ACTION POTENTIAL Defined as Rapid, transient & large changes in membrane potential resulting in reversal of polarity, which is conducted. Develops only at the threshold potential. Follows a ‘triggering event’(stimulus). Consists of rapid depolarization followed by rapid repolarization of membrane .

DEFINITIONS Polarized state Electrotonic potentials Depolarization Repolarization Hyperpolarization Threshold potential (Firing level) Spike potential

Polarized state ECF ICF ECF AXON +++++++++++++++++++++ - - - - - - - - - - - - - - - - - - AXON ICF Polarized state

mV -60 -70 -80 Threshold potential DEPOLARIZATION REPOLARIZATION RMP HYPERPOLARIZATION

Electrotonic potentials catelectrotonic anelectrotonic

Response of a Nerve fibre to subthreshold stimuli of various strengths Volt mv - 55 mv Threshold -70mv RMP Time in msecs

Local or Electrotonic potentials (GRADED) Names depending on the site: eg, receptor potential, synaptic potential, end plate potential -Not well propagated -Magnitude directly proportional to stimulus strength (GRADED) -Depolarozing (cathode) or hyperpolarizing(anode) -Summation possible -No threshold - No latent period -No refractory period

Configuration of monophasic AP from a single nerve fiber

Phases of an Action Potential Stimulus artifact Latent period A short phase of slow depolarization At a particular level of membrane potential (threshold level), there appears a sharp upstroke-the rate of depolarization is markedly increased called as Rapid depolarization.

The membrane potential reaches about +35 mv. There is a rapid down stroke- i.e rapid repolarization. The sharp upstroke and down stroke constitute a spike potential A brief period of “after-hyperpolarization” commonly follows the phase of repolarization i.e. the membrane potential falls even below the RMP Finally RMP is restored

Latent period It is the period between the stimulus artifact and beginning of depolarization Duration of Latent period determined by: 1.Distance between the stimulating electrodes and the recording electrodes 2. Rate of conduction of nerve impulse (velocity of conduction or speed of nerve)

Depolarization Depolarization up to 7mv by stimulus opens few Na+ channels. Depolarization of cell membrane up to 15 mV – i.e at memb pot. of -55 mV, the voltage -gated Na channels open fully The membrane potential at which Na+ channels fully open (-55 mV) is known as “firing level” Positively charged Na+ enter the cell, along electrical & chemical gradient. When inside is +35mv, influx of Na+ stops. Actual equilibrium potential for Na+ is +60 mv, reason why it doesn’t reach that level is, Na+ conductance is short lived due channels attaining inactivated state. And the gradient for net movement also reversed.

Ionic basis of nerve action potential Rapid depolarization: Opening of Voltage Gated Na+ channels Explosive increase in permeability at threshold level Na+ influx along electrochemical gradient Ra

(decreased membrane potential) POSITIVE FEEDBACK CYCLE Triggering event Depolarization (decreased membrane potential) Na+ influx Opening of voltage gated channels POSITIVE FEEDBACK CYCLE

Repolarization The repolarization is caused by opening of voltage-gated K+ channels K+ open slowly and close slowly The net movement of completes the process of repolarization (inside becomes negative) As the closure of K+ is slow process, repolarization goes further down, is followed by a small period of after-hyperpolarization. Now the Na+-K+ pump starts operating and bring Na+ and K+ back to the pre-action potential position

Characteristics of Action potential 1.Action potential follows all or none law. The height of an action potential is always same, irrespective of the strength of stimulus. (all) No action potential is produced if the stimulus is subthreshold (none) The voltage-gated Na+ channels open to the same extent if the stimulus is threshold or suprathreshold 2. Once generated, AP is conducted in the tissue

Criteria Graded Potential Action Potential Size 2.Polarity 3.Propagation 4. Summation 5. Threshold 6. Refractory Period Graded, depends on stimulus streg Depol or Hyper Not well propagated Possible Nil All or none Depolarization Well propagated Not possible 15 mV Depol Present

Initiation of action potentials in body In a sensory neuron, at the beginning of nerve fiber (at the first node of Ranvier if myelinated) by stimulation of sensory receptors. Triggering event is the ‘GENERATOR potential’. ‘GENERATOR potential’ is an example of graded potential.

Initiation of action potentials in a sensory neuron First node of Ranvier (ACTION POTENTIAL) To CNS Sensory receptor (GENERATOR POTENTIAL) Initiation of action potentials in a sensory neuron

Initiation of action potentials in body In a motor neuron (or in an interneuron), at the ‘initial segment’ by the synaptic activity at the dendrites. Triggering event is the Synaptic activity at the dendrites (or at the soma) that generates ‘Excitatory Post Synaptic Potentials’. ‘Excitatory Post Synaptic Potentials’ are examples of graded potentials.

Initiation of action potentials in a motor neuron Initial segment (ACTION POTENTIAL) To muscle Dendritic zone (EPSP) Initiation of action potentials in a motor neuron

Properties of nerve action potential Self propagation (non-decremental)- conduction types-point to point (in non myelinated) & saltatory (in myelinated nerve) All-or-None law Refractory period

Self propagation of action potential Action potential is propagated in an unmyelinated axon fiber by successive electrotonic depolarization to the threshold, of the membrane ahead of the action potential In a myelinated axon successive depolarization occurs at the nodes of Ranvier (Saltatory conduction).

Propagation of action potential (impulse) in non myelinated axon (top) myelinated axon (bottom)

Conduction What are the meanings of these terms ? Bidirectional Orthodromic conduction Antidromic conduction

All or none phenomenon- response to varying stimuli strength

Refractory period Period of non-responsiveness of membrane to another stimulus Two components Absolute refractory period Relative refractory period Ensures one-way propagation of action potential Also limits frequency of action potentials

Absolute refractory period interval during which second AP cannot be initiated, regardless the strength of stimulus/li. Occurs from firing level to 1/3 of repolarization phase. Due to inactivation of Na+ channel. Na+ channel will not open until membrane repolarizes.

Relative refractory period interval during which second AP may not be initiated, but still possible to be generated. Occurs from starting of 1/3 of repolarization phase to starting point of hyperpolarization phase. Due to delay in closing of voltage-gated K+ channel leads to more K+ efflux from cell - membrane potential lower than RMP.

Changes in excitability during an AP

So the excitability of the axon varies during Action potential Other factors influencing excitability are: Ions: calcium, potassium, Sodium Temperature Timing of stimulus Local anesthesia

Learning outcomes Describe phases of an Action Potential Describe the characteristics of an AP Differentiate Action potential & electrotonic potentials Describe propagation of AP along a myelinated & un myelinated nerve fiber Describe the properties of Action potential Describe changes in excitability during different phases of AP.