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Titolo:
Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and antiarrhythmic consequences
Autore:
Elias, CL; Lukas, A; Shurraw, S; Scott, J; Omelchenko, A; Gross, GJ; Hnatowich, M; Hryshko, LV;
Indirizzi:
Univ Manitoba, St Boniface Gen Hosp, Res Ctr, Inst Cardiovasc Sci, Winnipeg, MB R2H 2A6, Canada Univ Manitoba Winnipeg MB Canada R2H 2A6 ci, Winnipeg, MB R2H 2A6, Canada Hosp Sick Children, Div Cardiol, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
fascicolo: 3, volume: 281, anno: 2001,
pagine: H1334 - H1345
SICI:
0363-6135(200109)281:3<H1334:IONEBK>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
SODIUM-CALCIUM EXCHANGE; CARDIAC NA+-CA2+ EXCHANGER; RABBIT VENTRICULAR MYOCYTES; TRANSIENT INWARD CURRENT; SARCOLEMMAL CA-ATPASE; INDUCED HEART-FAILURE; STEADY-STATE; DYNAMIC PROPERTIES; METABOLIC INHIBITION; NA+;
Keywords:
sodium/calcium; NCX1.1; giant excised patch clamp; electrophysiology;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Hryshko, LV Univ Manitoba, St Boniface Gen Hosp, Res Ctr, Inst Cardiovasc Sci, 351 Tache Ave, Winnipeg, MB R2H 2A6, Canada Univ Manitoba 351 Tache Ave Winnipeg MB Canada R2H 2A6 Canada
Citazione:
C.L. Elias et al., "Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and antiarrhythmic consequences", AM J P-HEAR, 281(3), 2001, pp. H1334-H1345

Abstract

The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport,although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 muM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusionwere almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entryvia reverse Na+/Ca2+ exchange in this process.

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Documento generato il 06/04/20 alle ore 08:44:17