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Expression and Coexpression of CO2-sensitive Kir Channels in Brainstem Neurons of Rats

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Abstract

Several inward rectifier K+ (Kir) channels are inhibited by hypercapnic acidosis and may be involved in CO2 central chemoreception. Among them are Kir1.1, Kir2.3, and Kir4.1. The Kir4.1 is expressed predominantly in the brainstem. Although its CO2 sensitivity is low, coexpression of Kir4.1 with Kir5.1 in Xenopus oocytes greatly enhances the CO2/pH sensitivities of the heteromeric channels. If these Kir channels play a part in the central CO2 chemosensitivity, they should be expressed in neurons of brainstem cardio-respiratory nuclei. To test this hypothesis, we performed in-situ hybridization experiments in which the expression of Kir1.1, Kir2.3, Kir4.1 and Kir5.1, and coexpression of Kir4.1 and Kir5.1 were studied in brainstem neurons using non-radioactive riboprobes. We found that mRNAs of these Kir channels were present in several brainstem nuclei, especially those involved in cardio-respiratory controls. Strong labeling was observed in the locus coeruleus, ventralateral medulla, parabrachial-Kölliker-Fuse nuclei, solitary tract nucleus, and area postrema. Strong expression was also seen in several cranial motor nuclei, including the nucleus of ambiguus, hypoglossal nucleus, facial nucleus and dorsal vagus motor nucleus. In general, the expression of Kir5.1 and Kir4.1 was much more prominent than that of Kir1.1 and Kir2.3 in all the nuclei. Evidence for the coexpression of Kir4.1 and Kir5.1 was found in a good number of neurons in these nuclei. The expression and coexpression of these CO2/pH-sensitive Kir channels suggest that they are likely to contribute to CO2 chemosensitivity of the brainstem neurons.

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Acknowledgements

Special thanks to Drs. John Adelman at Oregon Health University, Steven C. Hebert at Yale University and Carol A. Vandenberg at University of California at Santa Barbara for their generosity in sharing the Kir4.1, Kir5.1, Kir1.1 and Kir2.3 cDNAs. The authors are grateful to Ying Wang for her technical assistance. This work was supported by RO1 grants (HL058410, HL067890) from the NIH. CJ was a Career Investigator of the American Lung Association.

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  1. Department of Biology, Georgia State University, 24 Peachtree Center Avenue Atlanta, GA 30302-4010, USA

    J. Wu, H. Xu, W. Shen & C. Jiang

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Wu, J., Xu, H., Shen, W. et al. Expression and Coexpression of CO2-sensitive Kir Channels in Brainstem Neurons of Rats . J. Membrane Biol. 197, 179–191 (2004). https://doi.org/10.1007/s00232-004-0652-4

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