We have recently shown that sulfur dioxide (SO2) derivatives (bisulfite and sulfite, 1:3 M/M) modulated L-type calcium, sodium, and potassium channels in rat myocytes. The aim of this study was to investigate whether SO2 derivatives could alter Na/Ca exchanger current and the intracellular free [Ca2+]. The nickel-sensitive Na/Ca exchanger current was measured in rat myocytes exposed to ramp pulses in Tyrode's solution containing ouabain, nifedipine, and +/- Ni (5 mmol/l). Myocytes were loaded with the fluorescent Ca2+ indicator Fura-2/AM to estimate intracellular Ca2+ concentration. SO2 derivatives significantly inhibited both outward and inward Ni-sensitive Na/Ca exchanger currents without a shift in the reversal potential. The intracellular free [Ca2+] was raised by SO2 derivatives in several concentrations. SO2 derivatives increased [Ca2+](i) in rat myocytes and its mechanism might involve SO2 derivatives significantly inhibiting Na/Ca exchanger current and enhancing L-type calcium channel. (C) 2007 Elsevier Inc. All rights reserved.