心筋Caチャンネルの細胞内調節機構
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概要
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Activity of the cardiac L-type Ca channels is regulated by extracellular signals such as β-adrenoceptor agonists, and phosphorylation hypothesis has been proposed for the mechanism of channel regulation. This hypothesis was assessed in single myocytes using the voltage-clamp and cell-dialysis methods. Internally applied cyclic AMP (cA MP) or A kinase mimicked the increasing effects of isoproterenol (ISO) on Ca current. Protein kinase inhibitor or protein phosphatases (type 1 and 2A) reversed ISO-enhanced Ca current to control levels. Incubation of Ca channels, which were reconstituted into liposomes, with A kinase increased the dihydropyridine-sensitive Ca efflux from liposomes, suggesting that phosphorylation of the Ca channel or a protein closely associated with the channel is responsible for the channel regulation. <BR>Acetylcholine (ACh) suppressed ISO-enhanced Ca current but not cAMP-or A kinase-enhanced Ca current suggesting that ACh acts at the level before action of cAMP, probably at adenylate cyclase. Consistently, the effect of ACh was abolished by pretreatment of the cells with pertussis toxin. <BR>It is concluded that phosphorylation of a membrane protein is a key mechanism for the regulation of the cardiac Ca channels by extracellular signals.
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