Modifications of human cardiac sodium channel gating by UVA light.
Voltage-gated Na(+) channels are membrane proteins responsible for the generation of action potentials. In this report we demonstrate that UVA light elicits gating changes of human cardiac Na+ channels. First, UVA irradiation hampers the fast inactivation of cardiac Nav1.5 Na(+) channels expressed in HEK293t cells. A maintained current becomes conspicuous during depolarization and reaches its maximal quasi steady-state level within 5-7 min. Second, the activation time course is slowed by UVA light; modification of the activation gating by UVA irradiation continues for 20 min without reaching steady state. Third, along with the slowed activation time course, the peak current is reduced progressively. Most Na(+) currents are eliminated during 20 min of UVA irradiation. Fourth, UVA light increases the holding current nonlinearly; this phenomenon is slow at first but abruptly fast after 20 min. Other skeletal muscle Nav1.4 isoforms and native neuronal Na(+) channels in rat GH(3) cells are likewise sensitive to UVA irradiation. Interestingly, a reactive oxygen metabolite (hydrogen peroxide at 1.5%) and an oxidant (chloramine-T at 0.5 mM) affect Na(+) channel gating similarly, but not identically, to UVA. These results together suggest that UVA modification of Na(+) channel gating is likely mediated via multiple reactive oxygen metabolites. The potential link between oxidative stress and the impaired Na(+) channel gating may provide valuable clues for ischemia/reperfusion injury in heart and in CNS.
Wang
G K
GK
Department of Anesthesia, Harvard Medical School and Brigham & Women's Hospital, 75 Francis St., Boston, MA 02115, USA.
Wang
S Y
SY
D000818:Animals; D002478:Cells, Cultured; D002700:Chloramines / Q000378:metabolism / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology* / Q000528:radiation effects*; D007668:Kidney / Q000502:physiology / Q000528:radiation effects; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D012680:Sensitivity and Specificity; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D014105:Tosyl Compounds / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014466:Ultraviolet Rays
D002700:Chloramines; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; C568322:Scn5a protein, rat; D015222:Sodium Channels; D014105:Tosyl Compounds; C016300:chloramine-T; D006861:Hydrogen Peroxide