Effect of Renal Ischemia/Reperfusion on Gene Expression of a pH-Sensitive K⁺ Channel

Abstract

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 ∼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. Conclusion: 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.

miR-182-5p Inhibition Ameliorates Ischemic Acute Kidney Injury

“…From the microarray data we selected two targets that were deregulated after ASO treatment which had at least one predicted binding site for miR-182-5p, based on three independent prediction algorithms (see Materials and Methods) and were associated with kidney injury in a literature research: Kcnj10 is a pH-sensitive K þ channel and mRNA levels are decreased after ischemia/reperfusion injury. 23 In our study miR-182-5p inhibition by ASO up-regulated Kcnj10 on both a gene expression as well as protein level. Fam129a (Niban) gene is associated with fibrosis in obstructive nephropathy 24 and was down-regulated by ASO treatment.…”

miRNA-Coordinated Networks as Promising Therapeutic Targets for Acute Kidney Injury

“…12 In addition, they show that these protective actions were associated with derepression of several genes previously related to kidney injury (K þ channel protein Kcnj10), fibrosis (Fam129a), and G 1 /S cell cycle control checkpoint genes in kidney disease (cyclin D). 13,14 Moreover, using pathway analysis in kidneys from ASO-treated rats and untreated controls, they identified cell proliferation to be among the most likely affected processes by miR-182-5p.…”

The role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss

“…Kir4.1 has extensive expressions in glial cells of the brain (Higashi et al, 2001; Seifert et al, 2009; Harada et al, 2013), kidney (Garcia et al, 2007), and inner ear (Hibino et al, 1997, 1999; Ando and Takeuchi, 1999; Takeuchi et al, 2001). …”