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The Journal of Neuroscience, August 1, 2000, 20(15):5689-5695
Viral Gene Transfer of Dominant-Negative Kv4 Construct Suppresses an O2-Sensitive K+ Current in Chemoreceptor Cells
M. Teresa Pérez-García1, 2, José Ramón López-López1, 2, Armenia M. Riesco1, 2, Uta C. Hoppe3, Eduardo Marbán3, Constancio González1, 2, and David C. Johns3 1 Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, 2 Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, 47005 Valladolid, Spain, and 3 Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Hypoxia initiates the neurosecretory response of the carotid body (CB) by inhibiting one or more potassium channels in the chemoreceptor cells. Oxygen-sensitive K+ channels were first described in rabbit CB chemoreceptor cells, in which a transient outward K+ current was reported to be reversibly inhibited by hypoxia. Although progress has been made to characterize this current with electrophysiological and pharmacological tools, no attempts have been made to identify which Kv channel proteins are expressed in rabbit CB chemoreceptor cells and to determine their contribution to the native O2-sensitive K+ current. To probe the molecular identity of this current, we have used dominant-negative constructs to block the expression of functional Kv channels of the Shaker (Kv1.xDN) or the Shal (Kv4.xDN) subfamilies, because members of these two subfamilies contribute to the transient outward K+ currents in other preparations. Delivery of the constructs into chemoreceptor cells has been achieved with adenoviruses that enabled ecdysone-inducible expression of the dominant-negative constructs and reporter genes in polycistronic vectors. In voltage-clamp experiments, we found that, whereas adenoviral infections of chemoreceptor cells with Kv1.xDN did not modify the O2-sensitive K+ current, infections with Kv4.xDN suppressed the transient outward current in a time-dependent manner, significantly depolarized the cells, and abolished the depolarization induced by hypoxia. Our work demonstrate that genes of the Shal K+ channels underlie the transient outward, O2-sensitive, K+ current of rabbit CB chemoreceptor cells and that this current contributes to the cell depolarization in response to low pO2.
Key words: O2-sensitive K+ current; viral gene transfer; dominant-negative constructs; carotid body chemoreceptors; hypoxia; potassium channels
Copyright © 2000 Society for Neuroscience 0270-6474/00/20155689-07$05.00/0
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