Alteration of arterial smooth muscle potassium channel composition and BKCa current modulation in hypertension
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We investigated K+ currents and their regulation by the sarcoplasmic reticulum in mesenteric arterial smooth muscle cells of the spontaneously hypertensive rat (SHR). Using perforated patch-clamp technique, we found the overall K+ current density was significantly lower in adult SHR compared to adult Wistar-Kyoto rats (WKY). The K+ currents were almost exclusively of large-conductance Ca2+-dependent (BK(Ca)) variety in SHR, but largely of voltage-gated (Kv) variety in WKY. Western blot assay showed parallel findings. These differences were not observed in pre-hypertensive rats. Depleting the intracellular Ca2+ store inhibited the K+ currents in adult SHR. Ryanodine augmented the K+ current at 1 microM, but suppressed it at 10 microM; 2-aminoethoxydiphenyl borate demonstrated concentration-dependent inhibition. We conclude that an alteration of membrane K+ channel composition has resulted in lower overall K+ current density. The changes in K+ current type may indicate an underlying defect in Ca2+-handling that predisposes smooth muscle cells to the hypertensive phenotype.
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