Hydrogen sulfide in combination with taurine or cysteic acid reversibly abolishes sodium currents in neuroblastoma cells.
Patch clamp studies of neuroblastoma cells have shown that in the presence of sodium hydrogen sulfide (NaHS; the in vitro precursor of H2S), addition of the sulfonated amino acids, taurine or cysteic acid resulted in reversible abolition of the inward sodium currents. This effect could also be demonstrated by preincubating cells for 3-20 min with 5-10 mM NaHS followed by replacement of the solution with taurine or cysteic acid in sulfide-free saline. Neither NaHS, taurine nor cysteic acid alone had any effect. The sulfhydryl reagents, beta-mercaptoethanol and dithiothreitol, were also found to abolish reversibly the sodium currents. As the effects of the above treatments were nearly identical, the synergistic action of NaHS with taurine or cysteic acid may result from reduction of the disulfide bonds between subunits comprising the sodium channel. The responses to NaHS and taurine, a putative neurotransmitter/neuromodulator, suggest that reductions in sodium channel function may be the mechanism(s) responsible for loss of central respiratory drive during H2S poisoning.
Warenycia
M W
MW
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Steele
J A
JA
Karpinski
E
E
Reiffenstein
R J
RJ
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003544:Cysteic Acid / Q000494:pharmacology*; D004357:Drug Synergism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects*; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D013654:Taurine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000603:Amino Acids, Sulfur; D015222:Sodium Channels; D013440:Sulfides; D013654:Taurine; D003544:Cysteic Acid; C025451:sodium bisulfide