Abstract
We investigated the mechanism by which α 1-adrenergic activation regulates basal and stimulated whole cell L-type Ca current (ICa) in rat ventricular myocytes using the physiological neurotransmitter, norepinephrine (NE, 10μM). Stimulation of α 1-adrenoceptors, achieved by NE+10μM esmolol (a β-receptor antagonist), had no significant effect on basal ICa. α 1-adrenergic activation had a marked inhibitory effect on ICa elevated by β activation (NE+1μM) prazosin, an α 1-receptor antagonist) or activation of adenylyl cyclase by forskolin (25μM); the inhibitory effect was reversible upon washout. However, α 1-adrenergic stimulation had no significant effect on ICa previously increased by intracellular application of cAMP (25μM). The inhibitory effect seen on ICa elevated by NE showed no significant shift of either I–V or inactivation curves. It is unlikely that the inhibitory effect of α 1-adrenergic stimulation on NE or forskolin-elevated ICa is mediated through activation of Ca-dependent protein kinase C or changes in intracellular free Ca (pCa=8.5, EGTA 5 mM) or cAMP-dependent phosphodiesterase. We conclude that α 1-adrenergic inhibition of β-adrenergic stimulated-ICa is probably mediated through an as yet unknown G-protein. This inhibitory effect could serve as a regulatory feedback mechanism in physiological and pathophysiological settings.
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References
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Boutjdir, M., Restivo, M., Wei, Y. et al. α 1- and β-adrenergic interactions on L-type calcium current in cardiac myocytes. Pflügers Arch 421, 397–399 (1992). https://doi.org/10.1007/BF00374231
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DOI: https://doi.org/10.1007/BF00374231