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Determinant Role of Membrane Helices in KATP Channel Gating

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Abstract

The ATP-sensitive K+ (KATP) channels couple chemical signals to cellular activity, in which the control of channel opening and closure (i.e., channel gating) is crucial. Transmembrane helices play an important role in channel gating. Here we report that the gating of Kir6.2, the core subunit of pancreatic and cardiac KATP channels, can be switched by manipulating the interaction between two residues located in transmembrane domains (TM) 1 and 2 of the channel protein. The Kir6.2 channel is gated by ATP and proton, which inhibit and activate the channel, respectively. The channel gating involves two residues, namely, Thr71 and Cys166, located at the interface of the TM1 and TM2. Creation of electrostatic attraction between these sites reverses the channel gating, which makes the ATP an activator and proton an inhibitor of the channel. Electrostatic repulsion with two acidic residues retains or even enhances the wild-type channel gating. A similar switch of the pH-dependent channel gating was observed in the Kir2.1 channel, which is normally pH- insensitive. Thus, the manner in which the TM1 and TM2 helices interact appears to determine whether the channels are open or closed following ligand binding.

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Acknowledgments

Special thanks to Dr. S. Seino at Chiba University in Japan and Dr. L Jan at California University at San Francisco for the gifts of Kir6.2 and Kir2.1 cDNAs, respectively. This work was supported by the NIH (HL058410, HL067890).

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  1. Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA, 30303-4010, USA

    R. Wang, A. Rojas, J. Wu, H. Piao, C. Y. Adams, H. Xu, Y. Shi, Y. Wang & C. Jiang

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  1. R. Wang
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Correspondence to C. Jiang.

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*These authors contributed equally to this work.

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Wang, R., Rojas, A., Wu, J. et al. Determinant Role of Membrane Helices in KATP Channel Gating. J Membrane Biol 204, 1–10 (2005). https://doi.org/10.1007/s00232-005-0741-z

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  • DOI: https://doi.org/10.1007/s00232-005-0741-z

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