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

I Dzhura, Y Wu, RJ Colbran, JR Balser… - Nature cell …, 2000 - nature.com
I Dzhura, Y Wu, RJ Colbran, JR Balser, ME Anderson
Nature cell biology, 2000nature.com
A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-
ion currents (I Ca) in response to increased intracellular Ca 2+ concentrations. The Ca 2+-
binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel
signature and the signalling events underlying Ca 2+/CaM-dependent facilitation are
unknown. Here we show that the Ca 2+/CaM-dependent protein kinase II (CaMK) is
necessary and possibly sufficient for I Ca facilitation. CaMK induces a channel-gating mode …
Abstract
A dynamic positive feedback mechanism, known as ‘facilitation’, augments L-type calcium-ion currents (I Ca) in response to increased intracellular Ca 2+ concentrations. The Ca 2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca 2+/CaM-dependent facilitation are unknown. Here we show that the Ca 2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for I Ca facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca 2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca 2+/CaM-dependent I Ca facilitation.
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