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 β-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 β-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 β-adrenergic receptor-mediated increase cell shortening, I_ca and cAMP production in male myocytes. Male myocytes were also found to have a higher β-adrenergic receptor density. These results suggest that cardiac myocytes from male rats have an enhanced response to β-adrenergic stimulation due to augmented β-adrenergic signaling that results in a greater transsarcolemmal Ca²⁺ influx.