Phosphorylation of Dihydropyridine-Sensitive Calcium Channels from Cardiac and Skeletal Muscle
The entry of Ca into many excitable cells occurs through voltage-dependent Ca channels that are activated in response to depolarization. An interesting aspect of some Ca channels is that in addition to their voltage dependence, they can be regulated by neurotransmitters. This has been most thoroughly characterized in electrophysiological studies of cardiac cells (Reuter, 1983; Tsienet al., 1986). The probability of opening of the predominant type of cardiac Ca channel, that which is sensitive to dihydropyridines (Niliuset al., 1985), is increased by norepinephrine and decreased by acetylcholine (Reuter, 1983; Heschleret al., 1986; Tsienet al., 1986). This regulation is believed to be mediated by cyclic AMP (cAMP) and to involve a cAMP-dependent phosphorylation of the channel itself or an associated regulatory protein (Reuter, 1983). A similar type of regulation by cAMP has also been observed with Ca channels in skeletal muscle and some neuronal preparations (Schmidet al., 1985; Chad and Eckert, 1986). The regulation of Ca channels by mechanisms implicating protein kinases other than cAMP-dependent protein kinase also has been reported (Di Virgilioet al., 1986; Paupardin-Tritschet al., 1986; Rane and Dunlap, 1986; Galizziet al., 1987; Stronget al., 1987). A goal of our laboratory is to elucidate the biochemical events involved in the regulation of Ca channels by phosphorylation-dependent processes. To this end we initiated studies with dihydropyridine-sensitive Ca channels from cardiac and skeletal muscle to determine if any of the peptide components of these channels serve as a substrate for cAMP-dependent, as well as Ca-dependent, protein kinases.
KeywordsAdenosine Sarcoma Polypeptide Trypsin Norepinephrine
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