Heteromeric Kir4.1/Kir5.1 inwardly rectifying potassium channels underlie the basolateral K⁺ conductance of renal distal convoluted tubular cells. Loss of function mutations of Kir4.1 (KCNJ10) subunit cause severe renal salt loss and extrarenal symptoms (EAST/SeSAME syndrome). A recent study provided evidence for a renal tubulopathy in Kir5.1^-/- mice (Paulais et al., 2011). Here, we investigated the relevance of the Kir5.1 subunit for the kidney function using a different conventional Kir5.1^-/- mouse.

Kir5.1^-/- mice thrived well, without growth retardation or apparent morphological abnormalities. Under normal diet, Kir5.1^-/- mice displayed normal arterial blood pressure levels and normal glomerular filtration rate compared to Kir5.1^+/+ mice. Plasma electrolyte and pH measurements of Kir5.1^-/- mice revealed disturbed electrolyte and acid-base balance: Adult Kir5.1^-/- mice showed hyposulfatemia, hyperchloremic hypokalemic metabolic acidosis, and slightly (but not significantly) increased plasma Na⁺ levels. Electrolyte measurements of urine revealed that Kir5.1^-/- mice lose more Mg²⁺ and Ca²⁺ via urine. In contrast to adult animals, young Kir5.1^-/- mice (before weaning) displayed a strongly diminished renal excretion of K⁺.

Our data indicate that Kir5.1 is an important determinant of renal electrolyte excretion and pH balance. Mutations of Kir5.1 could underlie renal salt wasting and hypochloremic acidosis in humans.