Calcium Channels Are Models of Self-Control

When Ca²⁺ ions flow through the pore of an individual voltage-gated Ca²⁺ channel, they act back on the channel they've passed through and alter subsequent Ca²⁺ flow. Such local, almost instantaneous regulation involves both positive and negative feedback mechanisms: Ca²⁺-dependent facilitation (CDF) and Ca²⁺-dependent inactivation (CDI), respectively. Indeed, some types of Ca²⁺ channel are capable of undergoing both CDF and CDI, with each form of modulation following a different time course and having a different dependency on the rate, extent, and spatial localization of Ca²⁺ entry. These channels are equipped with a special Ca²⁺-sensitive toolkit, which they use to exquisitely manipulate their own Ca²⁺ influx, and thereby adjust the many effector responses that lie downstream of the Ca²⁺ entry. Although such self-regulation has been recognized at the cellular level for decades (...