BK channels and a new form of hypertension.
Large, Ca-activated K channels (BK) are comprised of an α pore (BKα) and one of four β subunits (BKβ1-4). When the gene for BKβ1 is knocked out (BKβ1-KO), the result is increased myogenic tone of vascular smooth muscle and hypertension. We reexamined whether the hypertension is entirely due to increased vascular tone, because most monogenic forms of hypertension have renal origins and BKβ1 resides in renal connecting tubule (CNT) cells. Moreover, BKβ1 is localized in the adrenal glands, where it may control production of aldosterone. This review will summarize our report that a majority of the hypertension of BKβ1-KO is the result of insufficient handling of dietary K, resulting in increased plasma K and hyperaldosteronism, the latter promoting Na and fluid retention. The fluid retention and hypertension are exacerbated by a high-K diet and reduced by eplerenone, an aldosterone receptor inhibitor. Genetic knockout of BKβ4 (BKβ4-KO), which resides in intercalated cells, also exhibits deficient K excretion, fluid retention, and mild hypertension that is not exacerbated when animals are treated with a high-K diet. These results show that the hypertension associated with BKβ1-KO occurs because of enhanced fluid retention, as well as because of the previously described vascular dysfunction.
Grimm
P Richard
PR
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Sansom
Steven C
SC
D000313:Adrenal Medulla / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism
D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium