Cardiac-specific Overexpression of the a 1 Subunit of the L-type Voltage-dependent Ca 21 Channel in Transgenic Mice

The L-type voltage-dependent calcium channel (LVDCC) regulates calcium influx in cardiac myocytes. Activation of the b-adrenergic receptor (bAR) pathway causes phosphorylation of the L-VDCC and that in turn increases Ca 21 influx. Targeted expression of the L-VDCC a1 subunit in transgenic (Tg) mouse ventricles resulted in marked blunting of the bAR pathway. Inotropic and lusitropic responses to isoproterenol and forskolin in Tg hearts were significantly reduced. Likewise, Ca 21 current augmentation induced by isoproterenol and forskolin was markedly depressed in Tg cardiomyocytes. Despite no change in bAR 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 bAR by Ca 21 channels.