K ir 7.1 knockdown and inhibition alter renal electrolyte handling but not the development of hypertension in Dahl salt-sensitive rats.

High potassium supplementation is correlated with a lower risk of the composite of death, major cardiovascular events, and ameliorated blood pressure, but the exact mechanisms have not been established. Inwardly rectifying potassium (K) channels expressed in the basolateral membrane of the distal nephron play an essential role in maintaining electrolyte homeostasis. Mutations in this channel family have been shown to result in strong disturbances in electrolyte homeostasis, among other symptoms. K7.1 is a member of the ATP-regulated subfamily of K channels. However, its role in renal ion transport and its effect on blood pressure has yet to be established. Our results indicate the localization of K7.1 to the basolateral membrane of the aldosterone-sensitive distal nephron cells. To examine the physiological implications of K7.1, we generated a knockout of K7.1 ( in Dahl salt-sensitive (SS) rats and deployed chronic infusion of a specific K7.1 inhibitor, ML418, in wild-type Dahl SS strain. Knockout of resulted in embryonic lethality. Heterozygous rats revealed an increase in potassium excretion on a normal salt diet but did not exhibit a difference in blood pressure development or plasma electrolytes after three weeks of a high salt diet. Wild-type SS rats exhibited increased renal K7.1 expression when dietary potassium was increased. Potassium supplementation also demonstrated that rats excreted more potassium on normal salt. The development of hypertension was not different when challenged with high salt for three weeks, though rats excrete less sodium. Interestingly, chronic infusion of ML418 significantly increased sodium and chloride excretion after 14 days of high salt but did not alter salt-induced hypertension development. Here we find that reduction of K7.1 function, either through genetic ablation or pharmacological inhibition, can influence renal electrolyte excretion but not to a sufficient degree to impact the development of SS hypertension.