Calmodulin is required for a full activation of the calcium slow channels in heart cells.
The role of calmodulin in regulating the functioning of the calcium slow channels in cultured heart cell reaggregates was determined by using the liposome method for intracellular delivery of calmodulin, calmidazolium (calmodulin inhibitor), inhibitor of adenosine 3', 5'-cyclic monophosphate (cAMP)-dependent protein kinase (PrK), and the catalytic subunit of cAMP-dependent protein kinase. The cells exhibited a naturally-occurring slowly-rising action potential (APs) having a maximum rate of rise (+Vmax) of less than 25 V/s. Injection of calmodulin inhibitor (calmidazolium) blocked the spontaneously occurring slow APs and depolarized the membrane. Simultaneous injections of calmidazolium and the inhibitor of cAMP-dependent protein kinase further depolarized the membrane. Injection of calmodulin did not restore the slow APs, but a subsequent injection of the catalytic subunit of cAMP-dependent protein kinase did. If the catalytic subunit of cAMP-PrK was injected before the injection of calmodulin, the slow APs recovered only partially; full recovery of the slow APs required a subsequent injection of calmodulin. These findings suggest a potentiating effect of calmodulin in the regulation of myocardial slow calcium APs and thus suggest that the myocardial slow channels protein or an associated regulatory protein(s) must be phosphorylated by the Ca2+-calmodulin-dependent protein kinase and the catalytic subunit of cyclic AMP-dependent protein kinase in order to make the channel fully available for voltage activation.
Bkaily
G
G
Sperelakis
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002147:Calmodulin / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004594:Electrophysiology; D007473:Ion Channels / Q000378:metabolism*; D008081:Liposomes / Q000032:analysis; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000032:analysis; D011494:Protein Kinases / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D002147:Calmodulin; D007473:Ion Channels; D008081:Liposomes; D010713:Phosphatidylcholines; D013779:Tetrodotoxin; D011494:Protein Kinases