The effects of androgens on calcium homeostasis in card*
Principal Investigator: K L Golden
Abstract: DESCRIPTION (Applicant?s abstract) Aging is associated with a decline in circulating androgens and this corresponds to the onset of cardiac abnormalities including a decline in myocardial contractility in men. Our overlying hypothesis is that a reduction in androgens influences myosin heavy chain composition and calcium homeostasis in cardiac myocytes. Specific aim 1 will test the hypothesis that androgen reduction in gonadectomized animals produces altered calcium transients and depressed contractility of freshly dissociated cardiac myocytes. Specific aim 2 will test the hypothesis that a decrease in circulating androgens results in reduced mRNA and protein abundance for the calcium regulating proteins and a decline in the ratio of MHC-alpha to MHC-beta. The third specific aim will test the hypothesis that androgen treatment of cardiac myocytes in vitro reduces the ration of MHC-alpha to MHC-beta and increases mRNA and protein levels for the major Ca2+ regulatory proteins. Biophysical assessment of E-C coupling will be carried out in ventricular myocytes isolated from normal and castrated rats treated with and without androgens. Whole cell voltage clamp recordings, video edge-detection and Ca2+ fluorescence measurements will be used to compare calcium channels, Na/Ca exchange and to analyze sarco(endo)plasmic reticulum ATPase function. The abundance of myosin isoforms, mRNA and proteins for the calcium homeostatic proteins will be compared using standard molecular and cellular approaches. Taken together these experiments will allow us to ascertain whether the expression and function of calcium regulating proteins and myosin isoforms are regulated by androgens. The results of these experiments will shed light into the role of androgens in regulating cardiac contractile function.
Funding Period: 2001-08-08 - 2004-09-24
more information: NIH RePORT
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