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Titolo:
Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer
Autore:
Hoppe, UC; Marban, E; Johns, DC;
Indirizzi:
Johns Hopkins Univ, Inst Mol Cardiobiol, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 iobiol, Baltimore, MD 21205 USA
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 8, volume: 105, anno: 2000,
pagine: 1077 - 1084
SICI:
0021-9738(200004)105:8<1077:MDOCRB>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSIENT OUTWARD CURRENT; HEART-FAILURE; VENTRICULAR MYOCYTES; CURRENT-DENSITY; RAT VENTRICLE; K+ CHANNEL; EXPRESSION; CELLS; HETEROGENEITY; ADENOVIRUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Johns, DC Johns Hopkins Univ, Inst Mol Cardiobiol, Ross 844,720 Rutland Ave, Baltimore, MD 21205 USA Johns Hopkins Univ Ross 844,720 Rutland Ave Baltimore MD USA 21205
Citazione:
U.C. Hoppe et al., "Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer", J CLIN INV, 105(8), 2000, pp. 1077-1084

Abstract

Heart failure leads to marked suppression of the Ca2+-independent transient outward current (I-tol), but it is not clear whether I-tol downregulationsuffices to explain the concomitant action potential prolongation. To investigate the role of I-tol in cardiac repolarization while circumventing culture-related action potential alterations, we injected adenovirus vectors in vivo to overexpress or to suppress I-to1 in guinea pigs and rats, respectively. Myocytes were isolated 72 hours after intramyocardial injection and stimulation of the ecdysone-inducible vectors with intraperitoneal injection of an ecdysone analog. Kv4.3-infected guinea pig myocytes exhibited robust transient outward currents. Increasing density of I-tol progressively depressed the plateau potential in Kv4.3-infected guinea pig myocytes and abbreviated action potential duration (APD). In vivo infection with a dominant-negative Kv4.3-W362F construct suppressed peak I-tol in rat ventriculocytes, elevated the plateau height, significantly prolonged the APD, and resulted in a prolongation by about 30% of the QT interval in surface electrocardiogram recordings. These results indicate that I-tol plays a crucial role insetting the plateau potential and overall APD, supporting a causative rolefor suppression of this current in the electrophysiological alterations ofheart failure. The electrocardiographic findings indicate that somatic gene transfer can be used to create gene-specific animal models of the long QTsyndrome.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 09:15:41