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Pharmacologic Properties of the Swelling‐Induced Chloride Current of Dog Atrial Myocytes
Author(s) -
SOROTA STEVE
Publication year - 1994
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1994.tb01143.x
Subject(s) - niflumic acid , swelling , chloride channel , dids , chloride , pharmacology , patch clamp , medicine , biophysics , extracellular , channel blocker , biochemistry , chemistry , calcium , electrophysiology , biology , membrane , organic chemistry , pathology
Pharmacology of Swelling‐Induced Chloride Current. Introduction: Swelling‐induced chloride currents may contribute to cardiac electrical activity and cell volume regulation. Identification of selective Mockers would aid in understanding the functional contribution(s) of this current. Methods and Results: Dog atrial cells were used to investigate the pharmacologic properties of the swelling‐induced chloride current. Whole cell patch clamp was used. Swelling‐induced chloride current was activated by osmotic stress. Initially, the chloride selectivity and calcium independence of the swelling‐induced current in dog atrial cells was demonstrated. Subsequently, a number of putative chloride channel blockers were examined. Anthracene‐9‐earboxylic acid (1mM) and dideoxyforskolin (1000 μ) and extracellular cAMP (5mM) were found to partially inhibit the swelling‐induced chloride current (∼50%, 80%, and 10% inhibition, respectively). Niflumic acid (100 μ), nitrophenylpropylamino benzoate (NPPB; 10 to 40 μ), and (+) 2‐[(2‐cydopentyl‐6,7‐dichloro‐2,3‐dihydro‐2‐melhyl‐1‐oxy‐1H‐inden‐5‐yl)oxy] acetic acid (indanyloxyacetic acid; IAA‐94; 100 μ) could fully inhibit the swelling‐induced chloride current without decreasing cell size. DIDS (100 μ) and dinitrostilbene disulfonic acid (DNDS;5 mM) fully inhibited outward currents but only partially inhibited inward current. Conclusions: Niflumic acid, IAA‐94, and NPPB were identified as full blockers of cardiac swelling‐induced chloride current. Nonspecific effects were identified for each of the full blockers. Experiments that use these agents as functional antagonists should be carefully designed and interpreted with caution.