Action Potential

Ion Channels- Passive (non-gated) channels are open at all times, permitting ions to move across the membrane.- Voltage-gated channels contain a voltage sensitive string of amino acids that cause the channel pore to open or

close in response to changes in membrane voltage- Channel pumps are energy driven ion exporters and/or importers designed to maintain steady-state ion

concentrations. The Na-K exchange pump (usually referred to as sodium pump) is vital to maintenance of the resting membrane potential

- Transmitter-gated channels abound in postsynaptic membranes. Some are activated directly by transmitter molecules, others indirectly.

- Transduction channels are activated by peripheral sensory stimulation. Sensory nerve endings exhibit different stimulus specificities in different location, for example mechanical in muscle; tactile, thermal, or chemical in skin; acoustic in cochlea; vestibular in labyrinth; electromagnetic in the retina; gustatory in the tongue; olfactory in the upper part of the nasal mucous membrane.

Resting Membrane Potential- When a neuron is not sending a signal, it is “at rest.” When a neuron is at rest, the inside of the neuron is

negative relative to the outside.- The membrane potential of the resting neuron is generated primarily by differences in concentration of Na and K

ions dissolved in the aqueous environments of ECF and cytosol- The membrane potential ranges from -60mV to -80mV.

Resting Membrane Permeability K+ Ions

- The K concentration on either side of the cell membrane would be the same if there were no attraction exerted by the protein anions on the inside, and the repulsion exerted by the Na cations on the outside. Na+ Pump

- The Na+-K+ pump stabilizes the resting potential, because Na ions tend to lead inward and K to leak outward along their concentration gradient

- The channel admits 2 potassium ions for every 3 sodium ions exported- The movement of ions against the concentration gradient requires energy that is provided by ATPase

Response to Stimulation: Action Potential- Presynaptic neuron releases transmitter substance into the synaptic cleft by the arrival of action potentials, or

spikes- The transmitter crosses the synaptic cleft and activate receptors of the target neuron (postsynaptic) which

activate transmitter-gated ion channel- The activation of the ion channel alter the polarization of the target neuron- If it is inhibitory it hyperpolarizes (by opening of Cl- channel), if it is excitatory it depolarizes

Electrotonic Potentials- The initial target neuron response to excitatory stimulation is a local, graded or electrotonic potential- At a low frequency of stimulation, small, decremental waves of depolarization extend for 50-100µm along the

affected dendrites, dying away after 2-3ms- With increasing frequency, the waves undergo temporal summation to form progressively larger waves

continuing on over the surface of the soma, spatial summation occurs when waves traveling along two or more dendrites coalesce on the soma

- About 15mV of depolarization, to a value of -55mV, brings the neuron to threshold (firing level) at its most sensitive region, or trigger point, in the initial segment of the axon

- The initial segment is the first region to ‘give way’ at threshold voltage, because it is exceptionally rich in voltage-gated sodium channels

- When the level of depolarization (the generator potential) reaches threshold, nerve impulses in the form of action potentials are suddently fired off

- In sensory neurons of cranial and spinal nerve, the trigger zone generates what is known as the receptor potential

- The trigger zone of sensory neuron is exceptionally rich in the sensation-specific transduction channel- In the case of myelinated nerve fibers, the trigger point is easily identified: in multipolar neuron, it is

immediately proximal to the first myelinated nerve fibers, and in peripheral sensory neurons it is immediately distal to the final segment

The Shape of Action Potentials- When the local response to stimulation has depolarized the membrane to threshold, the sudden increase in

depolarization is brought about by the opening of voltage-gated sodium channels- Sodium entry produces further depolarization and the positive feedback causes the remaining sodium channels

of the trigger zone to open, driving the membrane charge to momentarily into a charge reversal (overshoot)- At this point, the sodium channels commence a progressive inactivation, and the voltage-gated potassium

channels are simultaneously triggered to open- Current flow switches from Na+ inflow to K+ outflow- The hyperpolarization phase (undershoot) is explained by the voltage-gated sodium channels being completely

inactivated prior to closure of the K+ channels- Any remaining inconsistency is adjusted by activity of the Na+-K+ pump- In the resting state, an activation gate in the midregion of both Na+ and K+ channel pores is closed- The Na+ channel is the first to respond at threshold, by opening its activation gate and allowing a torrential

inflow of Na+ ions down the concentration gradient- One millisecond later, a second, inactivation gate, in the form of a flap of globular protein, seals the exit into the

cytosol while the K+ channel pore is opening- When the membrane potential approaches normality, the sodium gating reverts to its resting inactive state- The action potential response to depolarization is all or none- It is different from graded potential is that it does not summate and it is not decremental- During the rising and early falling phases of the action potential, the neuron passes through an absolute

refractory period where it is incapable of initiating a second impulse because too many voltage-gated channels are already open

- This is followed by a relative refractory period where stimuli in excess of the standard 15mV requirement can elicit a response

- It is quite common for the generator potential to reach up to 35mV, triggering impulses at 50-100 impulses per second, expressed as 50-100 Hz

Propagation- Depolarization at the trigger zone is propagated (conducted) along the axon- The membrane immediately proximal is sufficiently refractory to resist depolarization, whereas that immediately

distal undergoes a local response (depolarization) progressing to firing level- This process continues distally along the stem axon and its branches, thereby conducting the action potential all

the way to the nerve terminals- Whereas conduction along unmyelinated nerve fibers is continuous, along myelinated fibers it is salutatory

(jumping)

- Myelin sheaths are effective insulators overlying the intermodal segments, whereas Na channels are very abundant at the nodes

- Accordingly, spike potentials are generated at each successive node, the positive current traveling along the axoplasm of the internode before exiting at the nex t node

- As the current travels back through the ECF to recharge the depolarized patch of membrane, withdrawal of positive charge causes the next node to depolarize