Effects of PFOS and PFOA on L-type Ca2+ currents in guinea-pig ventricular myocytes

被引:129
作者
Harada, K
Xu, F
Ono, K
Iijima, T
Koizumi, A [1 ]
机构
[1] Kyoto Univ, Sch Med, Dept Hlth & Environm Sci, Kyoto 606, Japan
[2] Akita Univ, Sch Med, Dept Pharmacol, Akita 010, Japan
关键词
perfluorooctane sulfonate; perfluorooctanoate; L-type calcium channel; guinea pig; ventricular myocyte; negatively charged amphiphile;
D O I
10.1016/j.bbrc.2005.01.163
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are amphiphiles found ubiquitously in the environment, including wildlife and humans, and are known to have toxic effects on physiological functions of various tissues. We investigated the effects of PFOS and PFOA on action potentials and L-type Ca2+ currents, I-CaL, in isolated guinea-pig ventricular myocytes using whole-cell patch-clamp recording. In current-clamp experiments, PFOS significantly decreased the rate of spike, action potential duration, and peak potential at doses over 10 mu M. In voltage-clamp experiments, PFOS increased the voltage-activated peak amplitude of I-CaL, and shifted the half-activation and inactivation voltages of I-CaL to hyperpolarization. PFOA had similar effects PFOS, but showed significantly lower potency. These findings are consistent with previous observations for anionic n-alkyl surfactants, suggesting that PFOS and PFOA may change membrane surface potential, thereby eliciting general effects on calcium channels. These findings provide further insights into the mechanisms of PFOA and PFOS toxicities. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:487 / 494
页数:8
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