Netticadan T, Kato K, Tappia P, Elimban V, Dhalla N S
Department of Physiology, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Biochem Biophys Res Commun. 1997 Sep 18;238(2):544-8. doi: 10.1006/bbrc.1997.7305.
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.
