ID: 10729190

The generation and propagation of an action potential within a single neuron

The resting neuron fires an action potential when stimuli (ligand, electric shock) are intense enough to
depolarize the membrane to the threshold potential (around -55 mV). A voltage sensor within the
voltage-dependent Na+ channels detects the shift and pulls the channel open. This transiently raises
the conductance for Na+ over the rising phase. Both Na+ concentration and electrochemical gradients
help to induce the cation influx. At the peak potential (40 mV), a “ball and chain”–structure swings to
inactivate the channel. The voltage-dependent K+ channels open to allow K+ to flow out down its
concentration and electrostatic gradients during the falling phase. After repolarization to -70 mV, the
potential undershoots, because the K+ channels are slower to react and have no inactivation gate (the
membrane almost reaches the equilibrium potential for K+, when no net K+ movement occurs). During
this last phase, called hyperpolarization, it is possible to elicit a new action potential (AP) using a
stronger stimulus. This is called the relative refractory period. During depolarization and repolarization
(absolute refractory period), no new AP can be generated, due to the Na+ channel inactivation. The
inactivation ensures that the amplitude is also fixed. As a result, AP occurs in an “all-or-none” fashion:
if threshold depolarization occurs, an AP of fixed size is generated and transmitted further.

The density of voltage-gated Na+ channels determines how the AP is transmitted in the neuron.
Because there are few such channels in dendrites, potential transmission is mostly passive, prone to
signal attenuation. The excitatory and inhibitory postsynaptic potentials passed down the dendrites
are summed at the axon hillock. If they reach the threshold excitation, an AP is generated at the initial
segment. This is then regenerated along the axon. The AP can only be conducted in one direction,
because the previous zone is in the absolute refractory period (ARP) of 1 ms. However, if the axon’s
middle is artificially stimulated, AP will propagate both ways. Still, it will only affect synaptic terminals.

The AP can propagate at different velocities along the axon membrane. The amount of time needed
to reach a constant voltage is termed the time constant (τm). This is the product of membrane
resistance (Rm) and capacitance (Cm). Therefore, to increase AP speed, Rm or Cm must decrease.
Given Cm is a biological constant, Rm can be reduced by increasing the density of voltage-dependent
Na+ channels. Because a high density is not energetically economical (since inflowing Na+ must be
pumped out by Na+/K+ ATPase), myelinated axons cluster these channels in the nodes of Ranvier,
found between myelinated segments. Here, the channels have to produce a higher current density,
because the passive core conductor under the myelin sheath gradually decreases the electrical
disturbance (known as decremental conductance). Myelin (secreted by oligodendrocytes in the
central nervous system and Schwann cells in the peripheral nervous system) thus acts as an
electrical insulator for the internode, within which the signal is transmitted at much higher velocity.
This explains the quick saltatory conduction of APs in myelinated axons (120 m/s). By contrast, APs
are regenerated at every adjacent region in unmyelinated axons, by local circuit currents.

Conduction velocity is also affected by axon diameter. Because conductance is proportional to the
cross-section area, a thicker axon fibre propagates AP faster than thin fibres.

Although APs have fixed waveform, stimulus intensity is encoded by AP frequency. The maximum
frequency is 1000 Hz, as it can overcome the hyperpolarization (1-4 ms) but not the ARP (1 ms).