KCNJ10 (Kir4.1) is expressed in the basolateral membrane of the cortical thick ascending limb

Abstract

The aim of the present study is to examine the role of Kcnj10 (Kir.4.1) in contributing to the basolateral K conductance in the cortical thick ascending limb (cTAL) using Kcnj10+/+ wild-type (WT) and Kcnj10−/− knockout (KO) mice. The patch-clamp experiments detected a 40- and an 80-pS K channel in the basolateral membrane of the cTAL. Moreover, the probability of finding the 40-pS K was significantly higher in the late part of the cTAL close to the distal convoluted tubule than those in the initial part. Immunostaining showed that Kcnj10 staining was detected in the basolateral membrane of the cTAL but the expression was not uniformly distributed. The disruption of Kcnj10 completely eliminated the 40-pS K channel but not the 80-pS K channel, suggesting the role of Kcnj10 in forming the 40-pS K channel of the cTAL. Also, the disruption of Kcnj10 increased the probability of finding the 80-pS K channel in the cTAL, especially in the late part of the cTAL. Because the channel open probability of the 80-pS K channel in KO was similar to those of WT mice, the increase in the 80-pS K channel may be achieved by increasing K channel number. The whole cell recording further showed that K reversal potential measured with 5 mM K in the bath and 140 mM K in the pipette was the same in the WT and KO mice. Moreover, Western blot and immunostaining showed that the disruption of Kcnj10 did not affect the expression of Na-K-Cl cotransporter 2 (NKCC2). We conclude that Kir.4.1 is expressed in the basolateral membrane of cTAL and that the disruption of Kir.4.1 has no significant effect on the membrane potential of the cTAL and NKCC2 expression.

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

“…First, expression of NCC was analyzed to assess changes in transporters mediating sodium absorption in DCTs. Since it was reported that Kcnj10 is expressed in the cortical part of the thick ascending limb of Henle's loop (TAL) (20,33), we also explored the abundance of the Na…”

Genetic causes of hypomagnesemia, a clinical overview

“…This protein is expressed in several tissues, including the central nervous system, inner ear and basolateral side of DCT cells and possibly also TAL cells (reviewed in [41, 42]). In the kidney it forms a basolateral K + channel that conducts outward K + currents, thus recycling the K + imported by the Na + -K + -ATPase.…”

Basolateral Kir4.1 activity in the distal convoluted tubule regulates K secretion by determining NaCl cotransporter activity

“…1C is a scheme showing the expression of NKCC2, NCC, ENaC and ROMK in the apical membrane of the cTAL, DCT and CNT/CCD, respectively. However, experiments performed in post-neonatal 9 day (p9) mice have showed that the expression of Kir4.1 in the cTAL is mainly limited in the late part of cTAL rather than in the whole length of the cTAL of the mouse kidney [27*]. Kir4.1 expression was also detected in human TAL, however, loss-of-function mutations of Kir4.1 in humans did not have phenotype of defective membrane transport in the TAL, suggesting that Kir4.1 function in the TAL may not be indispensable [21–23].…”

“…Kir4.1 expression was also detected in human TAL, however, loss-of-function mutations of Kir4.1 in humans did not have phenotype of defective membrane transport in the TAL, suggesting that Kir4.1 function in the TAL may not be indispensable [21–23]. The possibility that Kir4.1 function in the cTAL could be compensated is also supported by patch-clamp experiments performed in p9 neonatal Kcnj10 −/− mice demonstrating that the disruption of Kir4.1 stimulates the activity of Na + and Cl − -activated 80- to 150-pS K + channel (K ca 4.1 or slo 2.2) in the cTAL [27;28]. The upregulation of Na-activated 80–150 pS K channel in the TAL may be induced by high vasopressin level in p9 neonatal Kir4.1 knockout mice as evidenced by the finding that AQP2 expression was upregulated [29].…”