PKC-Independent Stimulation of Cardiac Na/Ca Exchanger by Staurosporine.

Ca(2+) transients by reverse mode of cardiac Na(+)/Ca(2+) exchanger (NCX1) were recorded in fura-2 loaded BHK cells with stable expression of NCX1. Repeated stimulation of reverse NCX1 produced a long-lasting decrease of Ca(2+) transients ('rundown'). Rundown of NCX1 was independent of membrane PIP(2) depletion. Although the activation of protein kinase C (PKC) was observed during the Ca(2+) transients, neither a selective PKC inhibitor (calphostin C) nor a PKC activator (PMA) changed the degrees of rundown. By comparison, a non-specific PKC inhibitor, staurosporine (STS), reversed rundown in a dose-dependent and reversible manner. The action of STS was unaffected by pretreatment of the cells with calphostin C, PMA, or forskolin. Taken together, the results suggest that the stimulation of reverse NCX1 by STS is independent of PKC and/or PKA inhibition.