Mechanisms for regulation of arterial tone by Ca2+-dependent K+ channels in hypertension

1. The membrane potential and reactivity of arterial smooth muscle cells is regulated by a variety of K+ channels, which are highly expressed in vascular smooth muscle membranes. 2. Of these K+ channel types, the high-conductance, Ca2+-dependent K+ channel appears to be up-regulated in arterial smooth muscle membranes from hypertensive animals. 3. Patch-clamp studies show that whole-cell membranes and membrane patches of arterial smooth muscle obtained from rats with genetic or renal hypertension show an increased macroscopic and single-channel Ca2+-activated K+ current. Pharmacological block of this K+ current profoundly constricts aortic, renal, mesenteric and femoral arteries obtained from the same hypertensive animals, suggesting that Ca2+-dependent K+ current is a critical determinant of resting membrane potential in arterial muscle exposed to elevated blood pressure. 4. Thus, K+ efflux through Ca2+-dependent K+ channels appears to constitute an important homeostatic mechanism for buffering increases in arterial reactivity in hypertension.