Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels

A dynamic positive feedback mechanism, known as 'facilitation', augments L- type calcium-ion currents (I-Ca) in response to increased intracellular Ca2 + concentrations. The Ca2+-binding protein calmodulin (CaM) has been implic ated in facilitation, but the single-channel signature and the signalling e vents underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possi bly sufficient for I-Ca facilitation. CaMK induces a channel-gating mode th at is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling even t in triggering Ca2+/CaM-dependent I-Ca facilitation.