Overexpression of the L-type calcium channel alpha1 subunit in mouse hearts blunts the beta-adrenergic receptor pathway, suggesting a regulatory link between Ca2+ channels and beta-adrenergic signaling.
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Does not inform clinical channel modulation; leaves open a regulatory link between L-VDCC alpha1 and beta-adrenergic signaling in cardiac models.
The L-type voltage-dependent calcium channel (L-VDCC) regulates calcium influx in cardiac myocytes. Activation of the beta-adrenergic receptor (betaAR) pathway causes phosphorylation of the L-VDCC and that in turn increases Ca(2+) influx. Targeted expression of the L-VDCC alpha(1) subunit in transgenic (Tg) mouse ventricles resulted in marked blunting of the betaAR pathway. Inotropic and lusitropic responses to isoproterenol and forskolin in Tg hearts were significantly reduced. Likewise, Ca(2+) current augmentation induced by iso- proterenol and forskolin was markedly depressed in Tg cardiomyocytes. Despite no change in betaAR number, isoproterenol-stimulated adenylyl cyclase activity was absent in Tg membranes and NaF and forskolin responses were reduced. We postulate an important pathway for regulation of the betaAR by Ca(2+) channels.
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Muth et al. (1999) studied this question.
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