α1-Adrenoceptor Subtypes Mediate Negative Inotropy in Myocardium from α1A/C-Knockout and Wild Type Mice

D. T. McCloskey, D. G. Rokosh, T. D. O'Connell, E. C. Keung, P. C. Simpson and A. J. Baker. α1-Adrenoceptor Subtypes Mediate Negative Inotropy in Myocardium from α1A/C-Knockout and Wild Type Mice. Journal of Molecular and Cellular Cardiology (2002) 34, 1007–1017. Cardiac α1-adrenoceptors (AR) have two predominant subtypes (α1A-AR and α1B-AR) however, their roles in regulating contraction are unclear. We determined the effects of stimulating α1A-AR (using the subtype-selective agonist A61603) and α1B-AR (using a gene knockout mouse lacking α1A-AR) separately, and together (using phenylephrine) on Ca2+ transients, intracellular pH, and contraction of mouse cardiac trabeculae. Stimulation of α1-AR subtypes separately or together caused a triphasic contractile response. After a transient (≈3%) force rise (phase 1), force declined markedly (phase 2), then partially recovered (phase 3). In phase 2, the force decline (% of initial) with combined α1A-AR plus α1B-AR stimulation (50±3%) was more than with separate subtype stimulation (P