OXIDANT STRESS INHIBITS NA-CA-EXCHANGE CURRENT IN CARDIAC MYOCYTES - MEDIATION BY SULFHYDRYL-GROUPS

The effects of oxidant stress (xanthine oxidase plus hypoxanthine or p hotoactivation of rose bengal) on the Na+-Ca2+-exchange current were s tudied in guinea pig ventricular myocytes with the use of voltage-clam p techniques. Oxidant stress depressed both the Ni2+-sensitive and ext racellular calcium concentration ([Ca2+](0))-activated current in a ti me-dependent manner (e.g., xanthine oxidase plus hypoxanthine inhibite d the Ni2+-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 Ni2+-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 elect rogenic Na+-Ca2+-exchange current seemed unchanged. Our results sugges t that oxidant stress causes a direct or indirect sulfhydryl group-med iated decrease of the Na+-Ca2+ exchanger.