Different effects of Calmodulin and Calmodulin kinase II on Ca²⁺-dependent facilitation and inactivation of Cardiac L-type Ca²⁺ channel

Abstract

Ca²⁺-dependent facilitation and inactivation are displayed in L-type Ca²⁺ channel in response to increased intracellular [Ca²⁺]i. CaM has been suggested to mediate the two autoregulatory feedbacks. We investigated this hypothesis using patch-clamp method (cell-attached mode) in guinea-pig ventricular myocytes. Ca²⁺ channnel activity was potentiated (facilitation) and then suppressed (inactivation) during continuous superfusion of high-Ca²⁺ solution. Both facilitation and inactivation were inhibited by CaM inhibitor, chlorpromazine (1, 10, 100μM) in a dose-dependent manner, implying that CaM is necessary for the two autoregulatory feedback mechanisms. On the other hand, CaMKII only affected the time course of facilitation and inactivation probably by slowing Ca²⁺ increase. These results suggest that CaM plays an important role in both facilitation and inactivation of cardiac L-type Ca²⁺ channel. [Jpn J Physiol 54 Suppl:S127 (2004)]