跳转至内容
Merck
  • Ranolazine attenuates hypoxia- and hydrogen peroxide-induced increases in sodium channel late openings in ventricular myocytes.

Ranolazine attenuates hypoxia- and hydrogen peroxide-induced increases in sodium channel late openings in ventricular myocytes.

Journal of cardiovascular pharmacology (2014-04-08)
Jihua Ma, Yejia Song, John C Shryock, Liangkun Hu, Weiping Wang, Xisheng Yan, Peihua Zhang, Luiz Belardinelli
摘要

Ranolazine attenuates cardiac arrhythmic activity associated with hypoxia and hydrogen peroxide (H2O2) by inhibition of late sodium current (late INa). The mechanism of ranolazine's action on Na channels was investigated using whole-cell and single-channel recording from guinea pig isolated ventricular myocytes. Hypoxia increased whole-cell late INa from -0.48 ± 0.02 to -3.99 ± 0.07 pA/pF. Ranolazine at 3 and 9 μmol/L reduced the hypoxia-induced late INa by 16% ± 3% and 55% ± 3%, respectively. Hypoxia increased the mean open probability and open time of Na-channel late openings from 0.016 ± 0.001 to 0.064 ± 0.007 milliseconds and from 0.693 ± 0.043 to 1.081 ± 0.098 milliseconds, respectively. Ranolazine at 3 and 9 μmol/L attenuated the hypoxia-induced increase of open probability by 19% ± 7% and 61% ± 1%, and increase of open time by 26% ± 19% and 74 ± 21%, respectively. H2O2 increased the mean open probability and open time of Na-channel late openings from 0.013 ± 0.002 to 0.107 ± 0.015 milliseconds and from 0.689 ± 0.075 to 1.487 ± 0.072 milliseconds, respectively. Ranolazine at 3 and 6 μmol/L reduced the H2O2-induced increase of mean open probability by 60% ± 7% and 95% ± 2%, and the increase of mean open time by 31% ± 21% and 82% ± 8%. In conclusion, the inhibition by ranolazine of hypoxia- and H2O2-stimulated late INa is due to reduction of both the open probability and open time of Na-channel late openings.

材料
货号
品牌
产品描述

Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
HEPES, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
牛磺酸, ≥99%
Sigma-Aldrich
HEPES缓冲溶液, 1 M in H2O
SAFC
HEPES
Sigma-Aldrich
牛磺酸, suitable for cell culture, meets USP testing specifications
Sigma-Aldrich
HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
SAFC
HEPES
Sigma-Aldrich
HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
Sigma-Aldrich
牛磺酸, BioUltra, ≥99.5% (T)
USP
牛磺酸, United States Pharmacopeia (USP) Reference Standard
SAFC
牛磺酸
Sigma-Aldrich
牛磺酸, ≥98%, FG
Supelco
牛磺酸, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
HEPES, anhydrous, free-flowing, Redi-Dri, ≥99.5%
Supelco
HEPES, Pharmaceutical Secondary Standard; Certified Reference Material