Mechanisms of sex differences in rat cardiac myocyte response to beta-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.
Vizgirda
Vida M
VM
Department of Medical Surgical Nursing, University of Illinois at Chicago, 845 S. Damen Ave., Chicago, IL 60612, USA.
Wahler
Gordon M
GM
Sondgeroth
Korie L
KL
Ziolo
Mark T
MT
Schwertz
Dorie W
DW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium