R. Harvey
Feb 1, 1993
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Journal
Pflügers Archiv
Abstract
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 β-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 β-adrenergic receptor. It is concluded that these stilbenedisulfonic acid derivatives are not effective antagonists of cAMP-activated Cl− channels in cardiac ventricular myocytes.