Figure 2.

Function and modulation of AIS ion channels. A, Schematic detailing roles of Na⁺ channel subtypes in AP initiation and backpropagation in neocortical pyramidal neurons. Accumulation of the low-threshold Na_V1.6 channels at the distal AIS determines the lowest threshold for AP initiation, whereas accumulation of the high-threshold Na_V1.2 channels at the proximal AIS promotes AP backpropagation to the soma and dendrites. B, Axonal K_V1 channels can shape the waveforms of axonal APs. Spreading of the somatic subthreshold depolarizations into the axon (top) may inactivate some axonal K_V1 channels (middle), increasing axonal AP duration (bottom). This in turn enhances neurotransmitter release. C, AIS low-voltage activated Ca²⁺ channels (Ca_V3) promote AP bursts in auditory brainstem interneurons. Their downregulation via local dopaminergic signaling suppresses spike output in response to somatic depolarization. DA, Dopamine.