Study on mechanism of modulation of cardiac L-type Ca^<2+> channel by phosphorylation and Ca^<2+>

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The major aim of the present study was to clarify the changes of the gating process of the cardiac L-type Ca^<2+> channels produced by channel phoisphorylation based on single channel analysis. During the course of the study, new problem of the involvement of Ca^<2+> channel beta-subunit on the phosphorylation-dependent modulation arised.Results1.Isoproterenolincreased mainly availability (Ps) and slightly openprobability (Po) of the L-type channel to increase the channel current. The increase of its concentration between 1 nM and 0.1 mM did not increase the rate of mode-2 sweeps.2.The rate of mode-2 sweeps in the presence of BAY K 8644 was significantly increased by isoproterenol.3.The time course of inactivation of macroscopic Ba^<2+> current was enhanced by nitrendipine and this was enhanced by isoproterenol.4.Treatment by beta-subunit antisence of cultured adult rabbit ventricular myocytes decreased the L-type current density by 30%, increased the time course of rise and decay of the current by a factor of two and significantly decreased the efficacy of isoproterenol to increase the current.Future prospectAccumulating knowledges from molecular biology study using heterologous expression system indicated the multisubuinit organization of L-type Ca^<2+> channels, phosphorylation sites in alpha-1 subunit and phosphorylation of beta subunit. Using antisence technology towards native cardiac myocytes and applying single channel recording technique we have a good chance to disclose the role of beta subunit in Ca^<2+> channel regulation.