Key result
Receptor occupation and membrane depolarization open separate Ca2+ channels in rabbit arterial smooth muscle, with sensitivity to Ca2+ antagonists varying inversely with intracellular Ca2+ release.
No immediate clinical implications from rabbit in vitro data; leaves open distinct Ca2+ pathways as potential therapeutic targets.
Evidence will be presented in support of the contention that receptor occupation and membrane depolarization open separate Ca2+ channels in rabbit aortic and mesenteric arteriolar smooth muscle. These channels can be differentially activated and inhibited, and the 45Ca influx through these channels is additive. The channels opened by receptor occupation (ROCs) appear to vary markedly among arteries in their sensitivity to organic Ca2+ antagonists, with greatest sensitivity in vessels wherein the release of intracellular Ca2+ by receptor occupation is least. Moreover, within the rabbit aorta, the sensitivity to Ca2+ antagonists is greater at lower rather than at higher concentrations of norepinephrine; this variation in Ca2+ antagonist sensitivity appears also to be inversely related to the degree of release of intracellular Ca2+ by norepinephrine. These observations have led to the hypothesis that the release of intracellular Ca2+ by agonists may decrease the sensitivity of ROCs to Ca2+ antagonists. Direct evidence in support of this hypothesis, however, remains to be obtained.
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Cauvin et al. (1985) studied this question. Ca2+ antagonists and norepinephrine was evaluated. Receptor occupation and membrane depolarization open separate Ca2+ channels in rabbit arterial smooth muscle, with sensitivity to Ca2+ antagonists varying inversely with intracellular Ca2+ release.
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