Mechanisms of sex differences in rat cardiac myocyte response to β-adrenergic stimulation

The purpose of this study was to investigate sex differences in the functional response of isolated rat heart ventricular myocytes to beta-adrenergic stimulation and in isoproterenol-stimulated signal transduction. Fractional shortening was measured using a video edge-detection system in control- and isoproterenol-stimulated myocytes that had been isolated from weight-matched rats. Number and affinity of the beta-adrenergic receptors and the L-type Ca(2+) channel were measured in ventricular cardiac membranes by radioligand binding studies. Control- and isoproterenol-mediated alteration in Ca(2+) current density (I(Ca)) was determined by patch clamping and cellular cAMP content was determined by radioimmunoassay. Study results demonstrate that female myocytes have higher Ca(2+) channel density and greater I(Ca) than male myocytes. However, isoproterenol elicits a greater beta-adrenergic receptor-mediated increase cell shortening, I(Ca) and cAMP production in male myocytes. Male myocytes were also found to have a higher beta-adrenergic receptor density. These results suggest that cardiac myocytes from male rats have an enhanced response to beta-adrenergic stimulation due to augmented beta-adrenergic signaling that results in a greater transsarcolemmal Ca(2+) influx.