PRESSURE-INDUCED ACTIVATION OF MEMBRANE K+ CURRENT IN RAT SAPHENOUS ARTERY

Pressurization of isolated arteries may result in Ca2+-dependent contraction and membrane depolarization. Because the open state probability of some vascular muscle K+ channels is augmented by rises in cytosolic Ca2+ and membrane depolarization, we investigated the possibility that increases in intraluminal pressure activate K+ channels in isolated, perfused rat saphenous arteries. Stepwise increases in intraluminal pressure from 5 to 205 mm Hg resulted in increasing, active arterial contraction, measured as smaller diameters in physiological salt solution than in Ca2+-free solution. Addition of 10 mM tetraethylammonium to the physiological salt solution to block arterial muscle K+ channels caused progressively greater diameter reductions at pressures above 25 mm Hg. Microelectrode measurements of membrane potential showed that tetraethylammonium depolarized arterial muscle more at 105 mm Hg (16+/-1 mV) than at 25 mm Hg (10+/-1 mV). The sensitivity of K+ current to tetraethylammonium was also demonstrated in patch-clamped vascular muscle cells from the same arteries. Peak whole-cell K+ current was suppressed 47% and 79% by 1 and 10 mM tetraethylammonium, respectively. This same current was enhanced 3.6 -fold by the Ca2+ ionophore A23187 (10-mu-M), suggesting a Ca2+ dependence. We conclude that increases in intraluminal pressure progressively activate tetraethylammonium-sensitive K+ channels in the arterial muscle membrane. This can serve as a negative feedback mechanism to limit pressure-induced arterial constriction.