Pharmacologic properties of the swelling-induced chloride current of dog atrial myocytes.
BACKGROUND
Swelling-induced chloride currents may contribute to cardiac electrical activity and cell volume regulation. Identification of selective blockers would aid in understanding the functional contribution(s) of this current.


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-carboxylic acid (1 mM) and dideoxyforskolin (100 microM) and extracellular cAMP (5 mM) were found to partially inhibit the swelling-induced chloride current (approximately 50%, 80%, and 10% inhibition, respectively). Niflumic acid (100 microM), nitrophenylpropylamino benzoate (NPPB; 10 to 40 microM), and (+) 2-[(2-cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxy-1H-inden -5-yl)oxy d acetic acid (indanyloxyacetic acid; IAA-94; 100 microM) could fully inhibit the swelling-induced chloride current without decreasing cell size. DIDS (100 microM) 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.
Sorota
S
S
Department of Pharmacology, Columbia University, New York, New York 10032.
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D016275:Atrial Function; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D006016:Glycolates / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D013267:Stilbenes / Q000494:pharmacology
D000873:Anthracenes; D018118:Chloride Channels; D006016:Glycolates; D009579:Nitrobenzoates; D013267:Stilbenes; D005576:Colforsin; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; C015765:MK 473; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; C010030:9-anthroic acid; C047983:1,9-dideoxyforskolin; D002118:Calcium