Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. Kir4.2 is an integral membrane protein and inward-rectifier type potassium channel. Kir4.2 has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Three transcript variants encoding the same protein have been found for this gene.
The existing literature describing KCNJ15 and Kir4.2 is sparse. In spite of some initial channel nomenclature confusion, in which the gene was referred to as Kir1.3 the channel was first cloned from human kidney by Shuck and coworkers in 1997. Shortly thereafter it was shown that mutation of an extracellular lysine residue resulted in 6-fold increase in K+ current. Two years later, in 1999, voltage clamp measurements in xenopusoocytes found that intracellular acidification decreased the potassium current of Kir4.2. Also activation of protein kinase C decreased the current although in a non-reversible fashion. Furthermore, it was found that coexpression with related potassium channel Kir5.1, changed these results somewhat, which the authors concluded was likely to be a result of heterodimerization. Further voltage clamp investigations found the exact pH sensitivity (pKa = 7.1), open probability (high) and conductance of ~25 pS. In 2007 the channel was found to interact with the Calcium-sensing receptor in human kidney, using a yeast-two-hybrid system. This co-localization was verified at the protein level using both immunofluorescence techniques and coimmunoprecipitation of Kir4.2 and the Calcium-sensing receptor. Also a mutational study of Kir4.2 has demonstrated that removal of a c-terminal tyrosine increased the K+ current more than 10-fold. Because the channel has a very high open probability, the authors of this last article conclude that this increase is mediated by increased trafficking of the protein to the membrane and not increased single-channel conductance. This same line of reasoning is applicable to the initial work of Derst and coworkers.
^Shuck ME, Piser TM, Bock JH, Slightom JL, Lee KS, Bienkowski MJ (1997). "Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3)". J. Biol. Chem. 272 (1): 586–593. doi:10.1074/jbc.272.1.586. PMID8995301.
^ abDerst C, Wischmeyer E, Preisig-Müller R, et al. (1998). "A hyperprostaglandin E syndrome mutation in Kir1.1 (renal outer medullary potassium) channels reveals a crucial residue for channel function in Kir1.3 channels". J. Biol. Chem. 273 (37): 23884–23891. doi:10.1074/jbc.273.37.23884. PMID9727001.
^Huang C, Sindic A, Hill CE, et al. (2007). "Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function". Am. J. Physiol. Renal Physiol. 292 (3): F1073–F1081. doi:10.1152/ajprenal.00269.2006. PMID17122384.