Larsen, C. K., Jensen, I. S., Sorensen, M. V., de Bruijn, P. I., Bleich, Markus, Praetorius, H. A. and Leipziger, J. (2016) Hyperaldosteronism after decreased renal K+ excretion in KCNMB2 knockout mice. American Journal of Physiology-Renal Physiology, 310 (10). F1035-F1046. DOI 10.1152/ajprenal.00010.2016.

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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 renal outer medullary K+ channel (K(ir)1.1) and by the Ca2+-activated K+ channel (K(Ca)1.1). Here, we report a novel knockout mouse of the beta(2)-subunit of the K(Ca)1.1 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 alpha-subunit of the K(Ca)1.1 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, beta(2)-independent mechanism. The phenotype of KCNMB2 mice was similar but milder than the phenotype of KCNMA1(-/-) mice.

Document Type:	Article
Additional Information:	Times Cited: 1 Larsen, Casper K. Jensen, Iben S. Sorensen, Mads V. de Bruijn, Pauline I. Bleich, Markus Praetorius, Helle A. Leipziger, Jens
Research affiliation:	Kiel University
Refereed:	Yes
Date Deposited:	07 Mar 2017 10:19
Last Modified:	01 Feb 2019 15:01
URI:	https://oceanrep.geomar.de/id/eprint/36184

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