Abstract

All Ca²⁺ channels are regulated by Ca²⁺, a feature that allows them to respond to their own activity and to the activities of neighboring Ca²⁺ channels. Inhibition by Ca²⁺ protects cells from potentially hazardous increases in cytosolic [Ca²⁺], and stimulation can mediate facilitation and regenerative propagation of Ca²⁺ signals. Calmodulin is emerging as a key player in regulation of Ca²⁺ channels by Ca²⁺, but its role is more complex and more beautiful than might have been imagined.