Hyperaldosteronism after decreased renal K+ excretion in KCNMB2 knockout mice.
The kidney is the primary organ ensuring K( homeostasis. K( is secreted into the urine in the distal tubule by two mechanisms: by the renal outer medullary K( channel (Kir1.1) and by the Ca(2+ activated K( channel (KCa1.1) Here, we report a novel knockout mouse of the b2 subunit of the KCa1.1 channel (KCNMB2) which displays hyperaldosteronism after decreased renal K( excretion. KCNMB2( mice displayed hyperaldosteronism, normal plasma K( concentration, and produced dilute urine with decreased K( concentration. The normokalemia indicated that hyperaldosteronism did not result from primary aldosteronism. Activation of the renin angiotensin aldosterone system was also ruled out as renal renin mRNA expression was reduced in KCNMB2( mice. Renal K( excretion rates were similar in the two genotypes; however, KCNMB2( mice required elevated plasma aldosterone to achieve K( balance. Blockade of the mineralocorticoid receptor with eplerenone triggered mild hyperkalemia and unmasked reduced renal K( excretion in KCNMB2( mice. Knockout mice for the a subunit of the KCa1.1 channel (KCNMA1( mice) have hyperaldosteronism, are hypertensive, and lack flow induced K( secretion. KCNMB2( mice share the phenotypic traits of normokalemia and hyperaldosteronism with KCNMA1( mice but were normotensive and displayed intact flow induced K( secretion. Despite elevated plasma aldosterone, KNCMB2( mice did not display salt sensitive hypertension and were able to decrease plasma aldosterone on a high Na( diet, although plasma aldosterone remained elevated in KCNMB2( mice. In summary, KCNMB2( mice have a reduced ability to excrete K( into the urine but achieve K( balance through an aldosterone mediated, b2 independent mechanism. The phenotype of KCNMB2 mice was similar but milder than the phenotype of KCNMA1( mice.
American journal of physiology. Renal physiology