Hyperaldosteronism after decreased renal K+ excretion in KCNMB2 knockout mice
| Autor: | Pauline I.A. de Bruijn, Mads V. Sorensen, Markus Bleich, Helle A. Praetorius, Iben Skov Jensen, Jens Leipziger, Casper Larsen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Medullary cavity Large-Conductance Calcium-Activated Potassium Channel beta Subunits Physiology Blood Pressure Urine Spironolactone Kidney 03 medical and health sciences Internal medicine Hyperaldosteronism KCNMB2 medicine Journal Article Animals Solute Carrier Family 12 Member 3 Epithelial Sodium Channels Aldosterone Mice Knockout Polyuria business.industry Renal K(+) excretion Sodium Dietary medicine.disease Eplerenone Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Knockout mouse Potassium Female business Homeostasis |
| Zdroj: | Larsen, C K, Jensen, I S, Sørensen, M V, de Bruijn, P I, Bleich, M, Prætorius, H & Leipziger, J 2016, ' Hyperaldosteronism after decreased renal K+ excretion in KCNMB2 knockout mice ', American Journal of Physiology: Renal Physiology, vol. 310, no. 10, pp. F1035-46 . https://doi.org/10.1152/ajprenal.00010.2016 |
| DOI: | 10.1152/ajprenal.00010.2016 |
| Popis: | 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 Ca2+-activated K+channel (KCa1.1). Here, we report a novel knockout mouse of the β2-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 α-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, β2-independent mechanism. The phenotype of KCNMB2 mice was similar but milder than the phenotype of KCNMA1−/−mice. |
| Databáze: | OpenAIRE |
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