Alteration of arterial smooth muscle potassium channel composition and BK sub(Ca) current modulation in hypertension

We investigated K super(+) 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 super(+) current density was significantly lower in adult SHR compared to adult Wistar-Kyoto rats (WKY). The K super(+) currents were almost exclusively of large-conductance Ca super(2+)-dependent (BK sub(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 Ca super(2+) store inhibited the K super(+) currents in adult SHR. Ryanodine augmented the K super(+) current at 1 mu M, but suppressed it at 10 mu M; 2-aminoethoxydiphenyl borate demonstrated concentration-dependent inhibition. We conclude that an alteration of membrane K super(+) channel composition has resulted in lower overall K super(+) current density. The changes in K super(+) current type may indicate an underlying defect in Ca super(2+)-handling that predisposes smooth muscle cells to the hypertensive phenotype.