α1-adrenergic stimulation increases ventricular action potential duration in the intact mouse heart

The role of alpha(1)-adrenergic receptors (a-ARs) in the regulation of myocardial function is less wellunderstood than that of beta-ARs. Previous reports in the mouse heart have described that alpha(1)-adrenergic stimulation shortens action potential duration in isolated cells or tissues, in contrast to prolongation of the action potential reported in most other mammalian hearts. It has since become appreciated, however, that the mouse heart exhibits marked variation in inotropic response to alpha(1)-adrenergic stimulation between ventricles and even individual cardiomyocytes. We investigated the effects of alpha(1)-adrenergic stimulation on action potential duration at 80% of repolarization in the right and left ventricles of Langendorff-perfused mouse hearts using optical mapping. In hearts under beta-adrenergic blockade (propranolol), phenylephrine or noradrenaline perfusion both increased action potential duration in both ventricles. The increased action potential duration was partially reversed by subsequent perfusion with the alpha-adrenergic antagonist phentolamine (1 mu mol L-1). These data show that alpha(1)-receptor stimulation may lead to a prolonging of action potential in the mouse heart and thereby refine our understanding of how action potential duration adjusts during sympathetic stimulation.