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, 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, β2-independent mechanism. The phenotype of KCNMB2 mice was similar, but milder than the phenotype of KCNMA1-/- mice.
- KCa1.1 channel
- potassium excretion
- Copyright © 2016, American Journal of Physiology - Renal Physiology