Kcnj10 encodes the inwardly rectifying K+ channel 4.1 (Kir4.1) and is expressed in the basolateral membrane of late TAL, DCT, CNT and CCD. In the present study, we perform experiments in p9 WT and Kcnj10-/- mice to examine the role of Kir.4.1 in contributing to the basolateral K+ conductance in the CNT and CCD, and to investigate whether disruption of Kir4.1 up-regulates ENaC expression. Immunostaining shows that Kir4.1 and Kir5.1 are expressed in the basolateral membrane of CNT and CCD. The patch-clamp studies detect three types of K+ channels (23 pS, 40 pS and 60 pS) in the basolateral membrane of the late CNT and initial CCD in the WT mice. However, only 23 pS and 60 pS K+ channels but not the 40 pS K+ channel were detected in Kcnj10-/- mice, suggesting that Kir.4.1 is a key component of the 40 pS K+ channel in the CNT/CCD. Moreover, the depletion of Kir.4.1 did not increase the probability of finding the 23 pS and 60 pS K+ channel in the CNT/CCD. We next used the perforated whole cell recording to measure the K+ reversal voltage in the CNT/CCD as an index of the cell membrane potential. Under control conditions, the K+ reversal potential was -69 mV in the WT mice and it was -61 mV in Kcnj10-/- mice. Western blotting and immunostaining showed that the expression of ENaC-β and ENaC-γ subunits from renal medulla section of Kcnj10-/- mice was significantly increased in comparison to that of WT mice. Also, the disruption of Kir4.1 increased AQP2 expression. We conclude that Kir4.1 is expressed in the CNT and CCD and partially participates in generating the cell membrane potential. Also, increased ENaC expression in medullary CD of Kcnj10-/- mice is a compensatory action in response to the impaired Na+ transport in the DCT.
- EAST syndrome
- Giltelman syndrome
- connecting tubule
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