Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
SODIUM-CHANNEL BLOCKADE REDUCES HYPOXIC SODIUM LOADING AND SODIUM-DEPENDENT CALCIUM LOADING
Autore:
HAIGNEY MCP; LAKATTA EG; STERN MD; SILVERMAN HS;
Indirizzi:
JOHNS HOPKINS UNIV HOSP,DIV CARDIOL,565 CARNEGIE BLDG,600 N WOLFE ST BALTIMORE MD 21205 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB BALTIMORE MD 21224 JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL BALTIMORE MD 21205
Titolo Testata:
Circulation
fascicolo: 1, volume: 90, anno: 1994,
pagine: 391 - 399
SICI:
0009-7322(1994)90:1<391:SBRHSL>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT VENTRICULAR MYOCYTES; ISOLATED RABBIT HEART; INTRACELLULAR SODIUM; CARDIAC MYOCYTES; CONTRACTILE FAILURE; NA+-CA-2+ EXCHANGE; OXYGEN PARADOX; ISCHEMIA; CELLS; REPERFUSION;
Keywords:
CALCIUM; SODIUM; CHANNELS; HYPOXIA; ISCHEMIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
M.C.P. Haigney et al., "SODIUM-CHANNEL BLOCKADE REDUCES HYPOXIC SODIUM LOADING AND SODIUM-DEPENDENT CALCIUM LOADING", Circulation, 90(1), 1994, pp. 391-399

Abstract

Background Studies have shown that the rise in intracellular ionized calcium, [Ca2+](i), in hypoxic myocardium is driven by an increase in sodium, [Na+](i), but the source of Na+ is not known. Methods and Results Inhibitors of the voltage-gated Na+ channel were used to investigate the effect of Naf channel blockade on hypoxic Na+ loading, Na+-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated adult rat cardiac myocytes. Single electrically stimulated (0.2 Hz) cellswere loaded with either SBFI (to index [Na+](i)) or indo-1. (to index[Ca2+](i)) and exposed to glucose-free hypoxia (Po-2 < 0.02 mm Hg). Both [Na+](i) and [Ca](i) increased during hypoxia when cells became inexcitable following ATP-depletion contracture. The hypoxic rise in [Na](i) and [Ca2+](i) was significantly attenuated by 1 mu mol/L R 56865. Tetrodotoxin (60 mu mol/L), a selective Na+-channel blocker, also markedly reduced the rise in [Ca2+](i) during hypoxia and reoxygenation. Reoxygenation-induced cellular hypercontracture was reduced from 83% (45 of 54 cells) under control conditions to 12% (4 of 32) in the presence of R 56865 (P < .05). Lidocaine reduced hypercontracture dose dependently with 13% of cells hypercontracting in 100 mu mol/L lidocaine,42% in 50 mu mol/L lidocaine, and 93% in 25 mu mol/L lidocaine. The Na+-K+ exchange blocker, ethylisopropylamiloride (10 mu mol/L) was alsoeffective, limiting hypercontracture to 12%. R 56865, lidocaine, and ethylisopropylamiloride were also effective in preventing hypercontracture in normoxic myocytes induced by 75 mu mol/L veratridine, an agentthat impairs Na+ channel inactivation. Ethylisopropylamiloride prevented the veratridine-induced rise in [Ca2+](i) without affecting Na+-Ca2+ exchange, suggesting that amiloride derivatives can reduce Ca2+ loading by blocking Na+ entry through Na+ channels, an action that may inpart underlie their ability to prevent hypoxic Na+ and Ca2+ loading. Conclusions Na+ influx through the voltage-gated Na+ channel is an important route of hypoxic Na+ loading, Na+-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated rat cardiac myocytes. Importantly, the Na+ channel appears to serve as a route for hypoxic Na+ influx after myocytes become inexcitable.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 16:23:54