Testosterone deprivation by castration impairs expression of voltage-dependent potassium channels in rat aorta

Abstract: In this study, we explored the effects of testosterone deprivation on the expression of voltage-dependent potassium (Kv) channels in vascular smooth muscle cells (VSMCs) in rats. Six months after mature male Wistar rats were castrated, functional and posttranscriptional alterations of voltage-dependent potassium channels were detected using isometric tension measurement, whole-cell patch-clamp and western blot analysis. Constriction of aortic artery rings in response to 4-aminopyridine was significantly decreased 6 months after castration. A significant decrease in the amplitude of voltage-dependent potassium currents of aortic artery smooth muscle cells was detected in castrated rats compared with control rats. The level of expression of Kv1.5 channel protein was decreased. The decreased function and suppressed Kv1.5 protein expression of Kv channels after castration were restored by testosterone replacement. We concluded that long-term deprivation of endogenous testosterone in rats significantly attenuated the function of voltage-dependent potassium channels, and that a decreased expression of Kv1.5 channel protein accounted for this alteration. Restoration of physiological concentrations of testosterone restored the impaired function of voltage-dependent potassium channels, which may provide evidence for the beneficial effects of clinical testosterone replacement. [Copyright &y& Elsevier]