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 (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for ICa facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent ICa facilitation.
Dzhura
I
I
Department of Anesthesiology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Wu
Y
Y
Colbran
R J
RJ
Balser
J R
JR
Anderson
M E
ME
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D020746:Calcium Channels, L-Type; D002147:Calmodulin; D004791:Enzyme Inhibitors; D010455:Peptides; D001464:Barium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium