Oxidant stress inhibits Na-Ca-exchange current in cardiac myocytes: mediation by sulfhydryl groups?
The effects of oxidant stress (xanthine oxidase plus hypoxanthine or photoactivation of rose bengal) on the Na(+)-Ca(2+)-exchange current were studied in guinea pig ventricular myocytes with the use of voltage-clamp techniques. Oxidant stress depressed both the Ni(2+)-sensitive and extracellular calcium concentration ([Ca2+]o)-activated current in a time-dependent manner (e.g., xanthine oxidase plus hypoxanthine inhibited the Ni(2+)-sensitive current at +60 mV from 6.81 +/- 3.24 to 5.54 +/- 0.48 pA/pF; n = 6; P < 0.05). This effect was independent of the [Ca2+] of the pipette solution. Diamide, an alkylating agent that modifies protein sulfhydryl groups, also decreased the Ni(2+)-sensitive current (at + 60 mV: from 5.76 +/- 1.55 to 3.43 +/- 0.99 pA/pF; n = 6; P < 0.05). The stoichiometry (n) and partition coefficient (gamma) of the electrogenic Na(+)-Ca(2+)-exchange current seemed unchanged. Our results suggest that oxidant stress causes a direct or indirect sulfhydryl group-mediated decrease of the Na(+)-Ca2+ exchanger.
Coetzee
W A
WA
Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Ichikawa
H
H
Hearse
D J
DJ
D000818:Animals; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D004553:Electric Conductivity; D006168:Guinea Pigs; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D008027:Light; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D012395:Rose Bengal / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013438:Sulfhydryl Compounds / Q000502:physiology*; D014969:Xanthine Oxidase / Q000494:pharmacology
D002352:Carrier Proteins; D007042:Hypoxanthines; D016877:Oxidants; D019831:Sodium-Calcium Exchanger; D013438:Sulfhydryl Compounds; D012395:Rose Bengal; D019271:Hypoxanthine; D009532:Nickel; D014969:Xanthine Oxidase; D002118:Calcium