Effects of PFOS and PFOA on L-type Ca2+ currents in guinea-pig ventricular myocytes.
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 Ca(2+) 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 microM. 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.
Harada
Kouji
K
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Xu
Feng
F
Ono
Kyoichi
K
Iijima
Toshihiko
T
Koizumi
Akio
A
D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D002210:Caprylates / Q000494:pharmacology*; D002478:Cells, Cultured; D005466:Fluorocarbons / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D016276:Ventricular Function
D017738:Alkanesulfonic Acids; D020746:Calcium Channels, L-Type; D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D002118:Calcium