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Titolo:
Blockade of cardiac ATP-sensitive K+ channel by cibenzoline targets its pore-forming subunit
Autore:
Horie, M; Watanuki, M; Tsuji, K; Ishida, H; Ishida-Takahashi, A; Yuzuki, Y; Seino, Y; Sasayama, S;
Indirizzi:
Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Sakyo Ku, Kyoto 606, Japan Kyoto Univ Kyoto Japan 606 pt Cardiovasc Med, Sakyo Ku, Kyoto 606, Japan Kyoto Univ, Grad Sch Med, Dept Metab & Clin Nutr, Kyoto 606, Japan Kyoto Univ Kyoto Japan 606 Med, Dept Metab & Clin Nutr, Kyoto 606, Japan
Titolo Testata:
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
fascicolo: 3, volume: 35, anno: 2000,
pagine: 434 - 442
SICI:
0160-2446(200003)35:3<434:BOCAKC>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC BETA-CELLS; EMBRYONIC KIDNEY-CELLS; SULFONYLUREA RECEPTOR; POTASSIUM CHANNELS; INSULIN-SECRETION; SKELETAL-MUSCLE; HEART-CELLS; ANTIARRHYTHMIC AGENT; MYOCARDIAL-ISCHEMIA; GUINEA-PIG;
Keywords:
antiarrhythmic agents; ion channels; ischemia; K-ATP channel; membrane permeability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Horie, M Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Sakyo Ku, Kyoto 606, Japan Kyoto Univ Kyoto Japan 606 vasc Med, Sakyo Ku, Kyoto 606, Japan
Citazione:
M. Horie et al., "Blockade of cardiac ATP-sensitive K+ channel by cibenzoline targets its pore-forming subunit", J CARDIO PH, 35(3), 2000, pp. 434-442

Abstract

Several antiarrhythmic agents with Na-channel blocking action have been shown to inhibit cardiac K-ATP channels. We used cibenzoline to examine its precise target sits using patch-clamp techniques and receptor binding assaysin guinea-pig ventricular myocytes. Exposure of myocytes to a glucose-freeperfusate containing 1 mM cyanide produced a time-dependent shortening of the action potential duration (APD) in the current-clamp mode. Cibenzoline (30 mu M) slowed the development of APD shortening (APD(90) to similar to 91% vs. similar to 55% control 16 min after metabolic inhibition) at pH(o) 7.4, but not at pH(o) 6.4 (to similar to 60%). The pinacidil (30 mu M)-induced K-ATP currents were inhibited by cibenzoline in a pH(o)-dependent manner: the higher the pH(o), the stronger the blocking effect of cibenzoline. The binding of [H-3]-labeled cibenzoline was prevented by cibenzoline, but not by glibenclamide. Alkalinization produces a higher concentration of the uncharged form of cibenzoline, which can more easily permeate the cell membrane than the charged form. In NIH3T3 cells stably expressing Kir6.1, a putative pore-forming subunit of K-ATP channel, cibenzoline but not glibenclamide inhibited the K conductance. Thus cibenzoline interacts with the channelpore-forming subunit of the K-ATP channel (Kir6.2), but not the sulfonylurea receptor, from the cytosolic side after it permeates into the cell interior via the membrane lipid bilayer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 21:31:15