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Titolo:
Amiloride derivatives are potent blockers of K-ATP channels
Autore:
Bollensdorff, C; Zimmer, T; Benndorf, K;
Indirizzi:
Univ Jena, Inst Physiol, Abt Herz Kreislauf Physiol, D-07740 Jena, GermanyUniv Jena Jena Germany D-07740 Kreislauf Physiol, D-07740 Jena, Germany
Titolo Testata:
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
fascicolo: 4, volume: 364, anno: 2001,
pagine: 351 - 358
SICI:
0028-1298(200110)364:4<351:ADAPBO>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC B-CELLS; CARDIAC MYOCYTES; NA+/H+ EXCHANGE; INHIBITION; ANALOGS; ISCHEMIA; MYOCARDIUM; CALCIUM; SERIES; MUSCLE;
Keywords:
K+ currents; ATP; ischemia; Na+/Ca2+-exchange; Na+/H+-exchange;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Benndorf, K Univ Jena, Inst Physiol, Abt Herz Kreislauf Physiol, D-07740 Jena, Germany Univ Jena Jena Germany D-07740 hysiol, D-07740 Jena, Germany
Citazione:
C. Bollensdorff et al., "Amiloride derivatives are potent blockers of K-ATP channels", N-S ARCH PH, 364(4), 2001, pp. 351-358

Abstract

In cardiomyocytes sarcolemmal K-ATP channels open massively when the cytosolic [ATP] drops into the range of tens of micromolar, as during acute ischemia. The diuretic drug amiloride and related derivatives are well established as drugs blocking the Na+/H+- and the Na+/Ca2+-exchange, protecting theischemic heart. Herein, the blocking action of amiloride and its derivatives 2', 4'-dichlorobenzamil (DCB) and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on K-ATP channels was tested. In inside-out patches of mouse cardiac myocytes, amiloride, DCB, and EIPA reversibly blocked the K-ATP channels with the IC50 values 102, 1.80, and 2.14 mu mol/l (-80 mV), respectively. SimilarIC50 values were obtained in recombinant channels when coexpressing the K(IR)6.2 subunit with one of the sulfonylurea receptors SUR1 and SUR2A. All three drugs also blocked currents generated by the C-terminus deletion mutant K(IR)6.2 Delta 26 in the absence of SUR. Amiloride blocked outward currents more effectively than inward currents whereas the block by DCB and EIPA was voltage independent. In cardiomyocytes, also whole-cell I-KATP was blocked by the three drugs. In conclusion, amiloride, EIPA, and DCB block the pore-forming K(IR)6.2 subunit of cardiac K-ATP channels with higher potency than the Na+/H+- and the Na+/Ca2+-exchange, precluding a specific block of the exchanges under ischemic conditions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 18:23:16