Role of BKCa and SKCa channels in testosterone-induced nitric oxide release from human coronary artery endothelial cells
Keywords:
Calcium-activated potassium channel, human coronary artery endothelial cell, nitric oxide calorimetric assay, testosteroneAbstract
Testosterone is suggested to have beneficial and protective roles on cardiovascular system including vasodilation and lowering of blood pressure. Testosterone has been suggested to induce nitric oxide (NO) release from endothelial cells of different vascular origins. Information from previous studies provided that testosterone induces activating phosphorylation of endothelial nitric oxide synthase (eNOS) by acting through surface androgen receptor (sAR) and activating Src/PI3K/Akt-dependent pathway. A recent electrophysiological study in our laboratory using whole-cell patch-clamp technique demonstrated that testosterone-induced current mainly passed through large- and small-conductance Ca2+-activated K+ (BKCa and SKCa, respectively) channels. However, the involvement of BKCa and SKCa channels in testosterone-induced NO release was not elucidated. We herein examined the effect of testosterone-induced NO release and part of its mediators. We demonstrated that testosterone achieves its effect by acting through sAR and causes a dose-dependent increase in NO release from human coronary artery endothelial cells (HCAECs). This enhanced NO release was not affected by inhibitors of Gαi/o or PKA. Interestingly, although inhibitors of either BKCa or SKCa channels did not alter the testosterone-induced NO release, the combination of both BKCa and SKCa channel blockers significantly abolished the effect. These data suggest that testosterone induces NO release from HCAECs and its Ca2+-dependent pathway requires either BKCa or SKCa channel to function properly.
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