The role of intracellular Mg^<2+> and its mechanism in the regulation of cardiac Ca channels

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This project revealed a great detail about action of intracellular Mg^<2+> on the L-type Ca channels in frog ventricular myocytes and indicated a physiological role of Mg^<2+> in the final step of the beta-adrenergic signal transduction pathway as follows.1.Decrease in the concentration of intracelluar Mg^<2+> ([Mg^<2+>]_i) down to 1 muM resulted in increase in L-type Ca current (I_<Ca>) up to 10 times of the control. This was not mediated through phosphorylation nor GTP-binding protein but possibly by direct biding of Mg^<2+> to the channel. I_<Ca>- [Mg^<2+>]_i relationship was obtained and this relationship indicated that 80-90% of channels are inactivated under phsyiological [Mg^<2+>]_i.2.Increase in the intracellular concentration of Ca^<2+> ([Ca^<2+>]_i) induce increase in I_<Ca>. This phenomenon is mediated through unblock of Mg^<2+> because Ca^<2+> competes for the site with Mg^<2+> and unbinds Mg^<2+>.3.Increase in I_<Ca> by reducing [Mg^<2+>]_i was inhibited in the presence of intracellular GTP.This phenomenon has been shown for the first time. The inhibition by GTP was not mediated through GTP-binding protein but by its direct binding to the channel competetively with Mg^<2+>.4.Phosphorylation of the L-type Ca channel altered the relationship between I_<Ca> and [Mg^<2+>]_i so that change in [Mg^<2+>]_i between 1muM and 1 mM did not induce change in I_<Ca> while I_<Ca> remained in the maximum value. This result provoked the idea that phosphorylation increases I_<Ca> by means of reducing the sensitivity of Ca channels to the blocking action of Mg^<2+> and, therefore, both channel phosphorylation and reduction of [Mg^<2+>]_i may share a common final step in modulation of the channel.