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

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.