The heteromeric inwardly-rectifying Kir4.1/Kir5.1 K+ channel underlies the basolateral K+ conductance in the distal nephron and is extremely sensitive to inhibition by intracellular pH (pHi). The functional importance of Kir4.1/Kir5.1 in renal ion transport has recently been highlighted by mutations in the human Kir4.1 gene (KCNJ10) which result in SeSAME/EAST syndrome, a complex disorder that includes salt wasting and hypokalaemic alkalosis (1). Here, we have examined the role of the Kir5.1 subunit, using mice we have previously created that have a targeted disruption of the Kir5.1 gene (Kcnj16) (2). Interestingly, we find that the Kir5.1-/- mice display a phenotype that is the opposite of that seen in SeSAME/EAST syndrome where the Kir4.1 subunit is dysfunctional and leads to an overall down-regulation of Kir4.1/Kir5.1 functional activity. We suggest that this mirror-like phenotype may be a consequence of the fact that the Kir5.1 subunit is absent in these mice, and that the remaining homomeric Kir4.1 subunits cause an increased K+ conductance due to their reduced pH-sensitivity. These results highlight the important role that heteromeric Kir4.1/Kir5.1 plays as a pH-sensitive regulator of salt transport in the distal convoluted tubule.
University of Oxford (2011) Proc Physiol Soc 23, PC317
Poster Communications: Mirror-like SeSAME/EAST renal phenotype in mice lacking the Kir5.1 (Kcnj16) K+ channel subunit
M. Paulais1, M. Bloch-Faure1, N. Picard1, T. Jacques1, S. Krishna Ramakrishnan1, M. Keck1, F. Sohet1, D. Eladari1, P. Houillier1, S. Lourdel1, J. Teulon1, S. J. Tucker2
1. UPMC Université Paris 06, Paris, France. 2. Dept Physics, University of Oxford, Oxford, United Kingdom.
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