Pharmacological studies on mechanisms involved in Ca2+ oscillations in rat megakaryocytes

Extracellular application of ATP evoked the oscillatory K+ currents (IKCa) reflecting oscillation in cytoplasmic Ca2+ concentration ([Ca2-]i) of megakaryocyte isolated from rat bone marrow. We have reported that the [Ca2+], oscillation was regulated by intracellular Ca(2+)-pumping activity (Uneyama H.C. Uneyama and N. Akaike, 1993, J. Biol. Chem. 268, 168). Here we found that the Ca2+ pump of the megakaryocyte could be divided into at least two classes according to the sensitivity to phosphorylation-modulating drugs. The effects of protein kinase C and cyclic AMP-dependent protein kinase are complementary, and the effect of Ca2+/calmodulin is independent of the above two kinases. In addition, this is the first report concerning the physiological regulation of Ca(2+)-ATPase in living cells.