Axon Initial Segment Ca2+ Channels Influence Action Potential Generation and Timing

SummaryAlthough action potentials are typically generated in the axon initial segment (AIS), the timing and pattern of action potentials are thought to depend on inward current originating in somatodendritic compartments. Using two-photon imaging, we show that T- and R-type voltage-gated Ca2+ channels are colocalized with Na+ channels in the AIS of dorsal cochlear nucleus interneurons and that activation of these Ca2+ channels is essential to the generation and timing of action potential bursts known as complex spikes. During complex spikes, where Na+-mediated spikelets fire atop slower depolarizing conductances, selective block of AIS Ca2+ channels delays spike timing and raises spike threshold. Furthermore, AIS Ca2+ channel block can decrease the number of spikelets within a complex spike and can even block single, simple spikes. Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca2+ channels at the site of spike initiation play a key role in generating and shaping spike bursts.