Inwardly rectifying K+ (Kir) channels in Drosophila -: A crucial role of cellular milieu factors for Kir channel function

Three cDNAs encoding inwardly rectifying potassium (Kir) channels were isolated from Drosophila melanogaster. The protein sequences of Drosophila KirI (dKirI) and dKirII are moderately (<44%) and dKirIII sequence is weakly (<27%) identical to human Kir channel subunits. During fly development, five dKir channel transcripts derived from three genes are differentially expressed. Whole mount in situ hybridizations revealed dKirI transcripts absent from embryos, but dKirII and dKirIII are expressed in the embryonic hind gut and in Malpighian tubules, respectively, thus covering the entire osmoregulatory system of the developing fly. In the head of adult flies, predominantly dKirII transcripts were detected. When expressed in Xenopus oocytes, dKir channel activity was only observed after amino acid substitutions in their cytosolic tails (e.g. exchange of a unique valine in the NH2 terminus). In contrast, heterologous expression of wild type dKirI and dYirII in Drosophila S2 cells readily evoked typical inwardly rectifying K+ currents, which were weakly sensitive to Ba2+. Thus, the specific milieu of insect cells provides a crucial cellular environment for proper function of dKir channels.