CYCLOSPORINE-A SELECTIVELY REDUCES THE FUNCTIONAL EXPRESSION OF KIR2.1 POTASSIUM CHANNELS IN XENOPUS OOCYTES

The immunosuppressant cyclosporin A (CsA) reduced the functional expre ssion of Kir2.1 potassium channels in Xenopus oocytes in a dose-depend ent manner with an IC50 Of 11 mu M when the oocytes mere incubated wit h CsA after RNA injection, FK506 was less effective than CsA; cyclospo rin H, a non-immunosuppressive derivative of CsA, did not have a signi ficant effect, CsA did not impair protein synthesis since other potass ium channel types (Kir1.1, Kv1.1, Kv1.4) were much less sensitive to C sA, Our results suggest that the functional expression of Kir2.1 chann els is facilitated by the peptidyl-prolyl isomerase cyclophilin, The o bservations illustrate a new role of CsA in regulation of membrane ion transport, and may provide an alternative explanation for CsA-induced side effects in clinical use. (C) 1998 Federation of European Biochem ical Societies.