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Titolo:
Viral gene transfer of dominant-negative Kv4 construct suppresses an O-2-sensitive K+ current in chemoreceptor cells
Autore:
Perez-Garcia, MT; Lopez-Lopez, JR; Riesco, AM; Hoppe, UC; Marban, I; Gonzalez, C; Johns, DC;
Indirizzi:
Univ Valladolid, Inst Biol & Genet Mol, Valladolid, Spain Univ ValladolidValladolid Spain st Biol & Genet Mol, Valladolid, Spain Fac Med, Dept Bioquim & Biol Mol & Fisiol, CSIC, Valladolid 47005, Spain Fac Med Valladolid Spain 47005 l & Fisiol, CSIC, Valladolid 47005, Spain Johns Hopkins Univ, Sch Med, Inst Mol Cardiobiol, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 iobiol, Baltimore, MD 21205 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 15, volume: 20, anno: 2000,
pagine: 5689 - 5695
SICI:
0270-6474(20000801)20:15<5689:VGTODK>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
CAROTID-BODY CHEMORECEPTORS; POTASSIUM CHANNELS; NEURONAL EXCITABILITY; MEMBRANE PATCHES; OXYGEN; RAT; EXPRESSION; MODULATION; MYOCYTES; SUBUNITS;
Keywords:
O-2-sensitive K+ current; viral gene transfer; dominant-negative constructs; carotid body chemoreceptors; hypoxia; potassium channels;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Perez-Garcia, MT Fac Med, Dept Fisiol, C-Ramon & Cajal 7, Valladolid 47005, Spain Fac Med C-Ramon & Cajal 7 Valladolid Spain 47005 , Spain
Citazione:
M.T. Perez-Garcia et al., "Viral gene transfer of dominant-negative Kv4 construct suppresses an O-2-sensitive K+ current in chemoreceptor cells", J NEUROSC, 20(15), 2000, pp. 5689-5695

Abstract

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 O-2-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 O-2-sensitive K+ current, infections with Kv4.xDN suppressed the transient outward current in a time-dependent manner, significantly depolarized thecells, and abolished the depolarization induced by hypoxia. Our work demonstrate that genes of the Shal K+ channels underlie the transient outward, O-2-sensitive, K+ current of rabbit CB chemoreceptor cells and that this current contributes to the cell depolarization in response to low pO(2).

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Documento generato il 25/09/20 alle ore 07:47:20