PHOSPHORYLATION OF CARDIAC NA-K+ ATPASE BY CA2+()CALMODULIN DEPENDENTPROTEIN-KINASE/

Na+-K+ ATPase is known to be involved in the transport of sodium and p otassium 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 th e sarcolemmal membrane, Incubation of cardiac sarcolemma in the presen ce of Ca2+ and calmodulin resulted in phosphorylation of a 110 kDa pro tein, 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 inhib itor of Na+-K+ ATPase, had no effect, Furthermore, phosphorylation of the sarcolemmal membrane with Ca2+/calmodulin caused significant reduc tion in the activity of Na+-K+ ATPase. These results suggest that phos phorylation of the alpha-subunit of Na+-K+ ATPase by an endogenous CaM kinase may lead to an inhibition of its catalytic activity. (C) 1997 Academic Press.