Effect of renal ischemia/reperfusion on gene expression of a pH-sensitive K+ channel.
BACKGROUND
Sodium reabsorption depends on the Na/K/ATPase activity coupled to basolateral K+ recycling through K+ channels. ATP depletion reduces pump activity and increases K+ leak resulting in transport dysfunction. Kir4.1 is a pH-sensitive K+ channel expressed in the basolateral membrane of distal tubules. In this study, we evaluated whether Kir4.1 is also expressed in proximal tubules (PTs) and whether renal ischemia alters Kir4.1 mRNA expression levels.


METHODS
The presence of Kir4.1 mRNA was evaluated in PTs microdissected from collagenase-treated rat kidneys. Kir4.1 expression levels were estimated in the renal cortex by multiplex RT-PCR after 30 or 60 min of renal ischemia followed by 1, 24, 48 or 72 h of reperfusion.


RESULTS
The PCR product obtained from isolated tubules was sequenced and showed approximately 98% homology with rat Kir4.1 cDNA. Ischemia/reperfusion for 30 min induced a time-dependent reduction in Kir4.1 mRNA expression in parallel with plasma creatinine, however recovery was delayed after 60 min of ischemia, remaining reduced after 72 h of reperfusion when plasma creatinine was already normalized.


CONCLUSIONS
Kir4.1 mRNA expression was decreased by renal ischemia. The ischemia-induced cellular K+ loss may be minimized by Kir4.1 downregulation and may contribute to the mechanism by which cellular acidification induces cell protection against ATP depletion.
Garcia
M A
MA
Disciplina de Nefrologia, Universidade Federal de São Paulo, São Paulo, Brasil.
Meca
R
R
Leite
D
D
Boim
M A
MA
D000818:Animals; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D014018:Tissue Distribution; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium