Hyperaldosteronism following decreased renal K+ excretion in KCNMB2 knock-out mice.

Hyperaldosteronism following decreased renal K+ excretion in KCNMB2 knock-out mice. Am J Physiol Renal Physiol. 2016 Mar 9;:ajprenal.00010.2016 Authors: Larsen CK, Jensen IS, Sorensen MV, de Bruijn PI, Bleich M, Praetorius HA, Leipziger J Abstract The kidney is the primary organ ensuring K(+) homeostasis. K(+) is secreted into the urine in the distal tubule by two mechanisms; by the ROMK channel (Kir1.1) by the KCa1.1 channel. Here we report a novel knock-out mouse of the β2 subunit (KCNMB2) of the KCa1.1 channel, which displays hyperaldosteronism following decreased renal K(+) excretion. KCNMB2(-/-) mice displayed hyperaldosteronism, normal plasma [K(+)] and produced dilute urine with decreased [K(+)]. The normokalemia indicated that hyperaldosteronism did not result from primary aldosteronism. Activation of the RAAS 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 hyperkalemia and unmasked reduced renal K(+) excretion in KCNMB2(-/-) mice. Mice lacking the α subunit of the KCa1.1 channel (KCNMA1(-/-)) have hyperaldosteronism, are hypertensive and lack flow-induced K(+) secretion. KCNMB2(-/-) share the phenotypic traits of normokalemia and hyperaldosteronism with KCNMA1(-/-) mice, bu...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research