Cyclosporin A selectively reduces the functional expression of Kir2.1 potassium channels in Xenopus oocytes

FEBS Letters

Hoshi, Toshinori²  Heinemann, Stefan H³  Kubo, Yoshihiro¹  Chen, Haijun³ 

[1]Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu-city, Tokyo 183, Japan

[2]Department of Physiology and Biophysics, The University of Iowa, Iowa City, IA 52242, USA

[3]Max-Planck-Gesellschaft, Arbeitsgruppe Molekulare und zelluläre Biophysik an der Friedrich-Schiller-Universität Jena, Drackendorfer Strasse 1, D-07747 Jena, Germany

关键词: Xenopus oocyte;    Immunosuppression;    Cyclosporin A;    Cyclophilin;    Peptidyl-prolyl isomerase;    Potassium channel;   

DOI  :  10.1016/S0014-5793(98)00028-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The immunosuppressant cyclosporin A (CsA) reduced the functional expression of Kir2.1 potassium channels in Xenopus oocytes in a dose-dependent manner with an IC₅₀ of 11 μM when the oocytes were incubated with CsA after RNA injection. FK506 was less effective than CsA; cyclosporin H, a non-immunosuppressive derivative of CsA, did not have a significant effect. CsA did not impair protein synthesis since other potassium channel types (Kir1.1, Kv1.1, Kv1.4) were much less sensitive to CsA. Our results suggest that the functional expression of Kir2.1 channels is facilitated by the peptidyl-prolyl isomerase cyclophilin. The observations 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.

【 授权许可】

Unknown