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Voltage-gated (Ca_v) Ca²⁺ channels are multi-subunit complexes that play diverse roles in a wide variety of tissues. A fundamental mechanism controlling Ca_v channel function involves the Ca²⁺ ions that permeate the channel pore. Ca²⁺ influx through Ca_v channels mediates feedback regulation to the channel that is both negative (Ca²⁺-dependent inactivation, CDI) and positive (Ca²⁺-dependent facilitation, CDF).

This review highlights general mechanisms of CDI and CDF with an emphasis on how these processes have been studied electrophysiologically in native and heterologous expression systems.

Electrophysiological analyses have led to detailed insights into the mechanisms and prevalence of CDI and CDF as Ca_v channel regulatory mechanisms. All Ca_v channel family members undergo some form of Ca²⁺-dependent feedback that relies …