The action potential in mammalian central neurons

Neuronal cell bodies in the mammalian CNS typically have more than a dozen distinct voltage-dependent conductances. The greater number of conductances compared to the squid axon is associated with much more complex firing patterns than can be produced by the squid axon.Action potential shapes and firing patterns differ widely among different types of neurons.One recognizable phenotype is that of fast-spiking neurons, which are capable of firing steadily at high frequencies and have narrow action potentials. This phenotype is typical of many interneurons and is associated with the expression of Kv3 family potassium channels.Some neurons with fast-spiking behaviour express resurgent sodium current, a component of tetrodotoxin-sensitive current that flows after the spike and promotes high-frequency firing.Most neurons have large calcium currents carried by multiple types of calcium channels. The calcium current is largest during the falling phase of the action potential but is often outweighed by calcium-activated potassium current, activated by extremely rapid coupling to calcium entry.Potassium channels commonly playing a major part in the repolarization of action potentials include Kv3 channels, IA (Kv4) channels, ID (Kv1) channels and large conductance calcium-activated potassium (BK) channels.Inactivation of potassium currents can produce frequency-dependent broadening of the action potential, which can produce synaptic facilitation. Potassium channels whose inactivation can lead to frequency-dependent spike broadening include BK channels and inactivating Kv1 family channels located in presynaptic terminals.Following the spike, many neurons have afterpotentials, including multiple types of afterhyperpolarizations with time courses lasting up to several seconds. Pyramidal neurons often have a prominent afterdepolarization which, if large enough, can lead to all-or-none bursting.Currents active at subthreshold voltages can greatly influence firing patterns and frequency. These include IA and ID potassium currents, steady-state “persistent” sodium current, T-type calcium current, and the hyperpolarization-activated cation current called Ih.The system of ionic currents that controls action potential shape and firing patterns in central neurons, although complex, has remarkable advantages for pursuing general problems in systems biology (such as robustness and redundancy): it has highly quantifiable elements, which are well-suited to mathematical modelling.