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 Ca2+ channel were measured in ventricular cardiac membranes by radioligand binding studies. Control- and isoproterenol-mediated alteration in Ca2+ 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 Ca2+ 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 Ca2+ influx.