内向き整流性K⁺チャネル(Kir7.1)阻害トランスジェニックマウスは、多飲により腎臓のK⁺排泄能不足を補っている

抄録

Recent data have shown that inward rectifier K⁺ channel Kir7.1, localized in the basolateral membrane of rat distal nephron (JASN 2000; 11; 1987-1994), may be involved in the development of renal K⁺ excretion (Kidney Int 2003; 63; 969-975). To further assess the role of Kir7.1 in kidney K⁺ excretion, we have generated transgenic (Tg) mice expressing dominant-negative mutant of Kir7.1 (dnKir7.1 Tg/+). Wild-type (WT) and dn Kir7.1 Tg mice were placed in metabolic cages and their water balance and urine osmolality and concentrations of urine electrolytes (Na⁺, K⁺, Cl⁻) were examined. Both WT and Tg mice fed a K⁺-free diet developed hypokalemia (2.4 and 1.7 mEq/l, respectively) at 3 days and after. Water intake was increased in WT, but not in Tg mice. On the other hand, Tg mice fed a normal diet demonstrated a significant polydipsia and polyuria, with a relatively lower urine osmolality as compared to WT mice. Further, urinary K⁺ excretion of WT and Tg mice increased in proportion to that their water increase. There was no significant difference in renal K⁺ excretion between WT and Tg mice. In conclusion, Tg mice being insufficient with the basolateral Kir7.1 of the kidney distal nephron probably drink more water to compensate for the ability to excrete a K⁺ load. [J Physiol Sci. 2006;56 Suppl:S82]