Phosphorylation of cardiac Na+-K+ ATPase by Ca2+/calmodulin dependent protein kinase.
Na+-K+ ATPase is known to be involved in the transport of sodium and potassium across the cell membrane. We describe here a novel mechanism for the regulation of cardiac Na+-K+ ATPase through phosphorylation by a Ca2+/calmodulin-dependent protein kinase (CaM kinase) present in the sarcolemmal membrane. Incubation of cardiac sarcolemma in the presence of Ca2+ and calmodulin resulted in phosphorylation of a 110 kDa protein, identified as the alpha-subunit of Na+-K+ ATPase. The compound W-7, a potent inhibitor of calmodulin, caused significant inhibition of the CaM kinase-mediated phosphorylation while ouabain, a potent inhibitor of Na+-K+ ATPase, had no effect. Furthermore, phosphorylation of the sarcolemmal membrane with Ca2+/calmodulin caused significant reduction in the activity of Na+-K+ ATPase. These results suggest that phosphorylation of the alpha-subunit of Na+-K+ ATPase by an endogenous CaM kinase may lead to an inhibition of its catalytic activity.
Netticadan
T
T
Department of Physiology, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Kato
K
K
Tappia
P
P
Elimban
V
V
Dhalla
N S
NS
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D010766:Phosphorylation; D051381:Rats; D012508:Sarcolemma / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D013449:Sulfonamides; C017967:W 7; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase