Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC317
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 Universit
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.
Where applicable, experiments conform with Society ethical requirements