Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH
Autore:
Yang, ZJ; Xu, HX; Cui, NG; Qu, ZQ; Chanchevalap, S; Shen, WZ; Jiang, C;
Indirizzi:
Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA Georgia State Univ Atlanta GA USA 30303 Dept Biol, Atlanta, GA 30303 USA
Titolo Testata:
JOURNAL OF GENERAL PHYSIOLOGY
fascicolo: 1, volume: 116, anno: 2000,
pagine: 33 - 45
SICI:
0022-1295(200007)116:1<33:BAMMUT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECTIFIER POTASSIUM CHANNELS; K-ATP CHANNELS; INTRACELLULAR PH; IDENTIFICATION; EXPRESSION; CLONING; SENSITIVITY; FAMILY; CELLS; PIP2;
Keywords:
CO2 chemoreception; pH; phosphatidylinositol-4,5-bisphosphate; excised patch; brainstem;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Jiang, C Georgia State Univ, Dept Biol, 24 Peachtree Cent Ave, Atlanta, GA30303 USA Georgia State Univ 24 Peachtree Cent Ave Atlanta GA USA 30303 USA
Citazione:
Z.J. Yang et al., "Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH", J GEN PHYSL, 116(1), 2000, pp. 33-45

Abstract

CO2 chemoreception may be related to modulation of inward rectifier K+ channels (Kir channels) in brainstem neurons. Kir4.1 is expressed predominantly in the brainstem and inhibited during hypercapnia. Although the homomericKir4.1 only responds to severe intracellular acidification, coexpression of Kir4.1 with Kir5.1 greatly enhances channel sensitivities to CO2 and pH. To understand the biophysical and molecular mechanisms underlying the modulation of these currents by CO2 and pH, heteromeric Kir4.1-Kir5.1 were studied in inside-out patches. These Kir4.1-Kir5.1 currents showed a single channel conductance of 59 pS with open-state probability (P-open) similar to 0.4 at pH 7.4. Channel activity reached the maximum at pH 8.5 and was completely suppressed at pH 6.5 with pKa 7.45. The effect of low pH on these currents was due to selective suppression of P-open without evident effects on single channel conductance, leading to a decrease in the channel mean open time and an increase in the mean closed time. At pH 8.5, single-channel currents showed two sublevels of conductance at similar to 1/4 and 3/4 of the maximal openings. None of them was affected by lowering pH. The Kir4.1-Kir5.1 currents wee modulated by phosphatidylinositol-4,5-bisphosphate (PIP2) that enhanced baseline P-open and reduced channel sensitivity to intracellular protons. In the presence of 10 mu M PIP2, the Kir4.1-Kir5.1 showed a pKa value of 7.22. The effect of PIP2, however, was not seen in homomeric Kir4.1 currents. The CO2/pH sensitivities were related to a lysine residue in the NH2 terminus of Kir4.1. Mutation of this residue (K67M, K67Q) completely eliminated the CO2 sensitivity of both homomeric Kir4.1 and heteromeric Kir4.1-Kir5.1. In excised patches, interestingly, the Kir4.1-Kir5.1 carrying K67M mutation remained sensitive to low pH(i). Such pH sensitivity, however,disappeared in the presence of PIP2. The effect of PIP2 on shifting the titration curve of wild-type and mutant channels was totally abolished when Arg178 in Kir5.1 was mutated. Thus, these studies demonstrate a heteromeric Kir channel that can be modulated by both acidic and alkaline pH, show the modulation of pH sensitivity of Kir channels by PIP2, and provide information of the biophysical and molecular mechanisms underlying the Kir modulation by intracellular protons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 04:19:59