Effects of stilbenedisulfonic acid derivatives on the cAMP-regulated chloride current in cardiac myocytes.
Stilbenedisulfonic acid derivatives have been shown to block Cl- channels directly in many different preparations. Therefore, the utility of these compounds as tools for studying the cAMP-dependent Cl- current (ICl) in guinea-pig ventricular myocytes was examined using the patch-clamp technique to record whole-cell Cl- currents at room temperature. It was found that 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) increased, rather than decreased, the isoproterenol (ISO)-activated Cl- current. However, SITS alone stimulated little or no sustained current, suggesting that SITS activates the Cl- current through a synergistic effect with ISO. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) also enhanced the ISO-activated Cl- current. However, 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) did not have any effect. SITS also exhibited a synergistic effect on the ISO-enhanced Ca2+ current in the same cells, suggesting that it affects the pathway involved in beta-adrenergic regulation of both Cl- and Ca2+ channels. SITS had no effect on the Cl- current stimulated by direct activation of adenylate cyclase with forskolin or exposure to the membrane-permeable cAMP derivative 8-bromoadenosine 3',5'-cyclic monophosphate. This suggests that SITS and DIDS may enhance the ISO-activated Cl- current via an effect on the beta-adrenergic receptor. It is concluded that these stilbenedisulfonic acid derivatives are not effective antagonists of cAMP-activated Cl- channels in cardiac ventricular myocytes.
Harvey
R D
RD
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D018118:Chloride Channels; D000242:Cyclic AMP / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
D015220:Calcium Channels; D018118:Chloride Channels; D008565:Membrane Proteins; D013267:Stilbenes; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; D000242:Cyclic AMP; D007545:Isoproterenol; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid