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

Although 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.