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Titolo:
Inhibition of L-type Ca2+ channel current in Xenopus oocytes by amiodarone
Autore:
Ding, SL; Chen, FH; Klitzner, TS; Wetzel, GT;
Indirizzi:
Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA
Titolo Testata:
JOURNAL OF INVESTIGATIVE MEDICINE
fascicolo: 4, volume: 49, anno: 2001,
pagine: 346 - 352
SICI:
1081-5589(200107)49:4<346:IOLCCC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CALCIUM-CHANNEL; MYOCYTES; THERAPY; SUBUNIT;
Keywords:
antiarrhythmic agent; Ca2+ current; amiodarone; signal pathway; Ca2+ channel subunit;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Wetzel, GT Univ Calif Los Angeles, Sch Med, 675 CE Young Dr S,3754 MRL, Los Angeles, CA 90095 USA Univ Calif Los Angeles 675 CE Young Dr S,3754 MRL Los Angeles CA USA 90095
Citazione:
S.L. Ding et al., "Inhibition of L-type Ca2+ channel current in Xenopus oocytes by amiodarone", J INVES MED, 49(4), 2001, pp. 346-352

Abstract

Background: Although amiodarone has been referred to as a class III antiarrhythmic agent, it also possesses electrophysiologic characteristics of thethree other classes (classes I and TV and minor class II effects). Previous studies have demonstrated that amiodarone inhibits Ca2+ channel current in intact cardiac myocytes. However, it is not clear whether this response reflects a pure class IV effect (direct Ca2+ channel inhibition) or a class II effect (beta -adrenergic receptor blockade) of amiodarone. Methods: In the current study, the effects of amiodarone on Ca2+ current were studied in the absence of sympathetic regulation using a Xenopus oocyteexpression system. The L-type Ca2+ channel alpha (1C) suhunit was coexpressed with the alpha (2 delta) and beta (2a) subunits in enzymatically digested Xenopus oocytes. Ca2+ currents were recorded using the cut-open oocyte preparation. Results: We found that perfusion of 10 muM isoproterenol produced no significant change in peak Ca2+ current (from 223 +/- 33 to 210 +/- 29 nA, mean /- SEM, n=5, P=not significant), indicating the absence of a functional stimulatory sympathetic signal pathway in these oocytes, After 10 minutes of exposure to 10 muM amiodarone, Ca2+ current amplitude was significantly decreased from 174 +/- 33 to 100 +/- 26 nA (n=8, P <0.01; control group: 220 +/- 33 to 212 +/- 29 nA, n=5, P=not significant). These effects were similarto those of 10 muM nifedipine (201 +/- 48 to 108 +/- 48 nA, n=6, P <0.05),a typical Ca2+ channel blocker. On the other hand, neither amiodarone nor nifedipine significantly altered the Ca2+ current activation or inactivation kinetics. Conclusions: These results demonstrate that amiodarone inhibits Ca2+ current in the absence of a functional intrinsic beta -adrenergic stimulatory system and, therefore, represents a true class IV effect.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:35:11