Article date: August 1999
By: Gregory M Dick, In Deok Kong, Kenton M Sanders, in Volume 127, Issue 8, pages 1819-1831
Volume‐Sensitive, Outwardly Rectifying (VSOR) Cl− currents were measured in canine colonic myocytes by whole‐cell patch clamp. Decreasing extracellular osmolarity 50 milliosmoles l−1 activated current that was carried by Cl− and 5–7 times greater in the outward direction.
Niflumic acid, an inhibitor of Ca2+‐activated Cl− channels, did not inhibit VSOR Cl− current. Glibenclamide, an antagonist of CFTR, and anthracene‐9‐carboxylate (9‐AC) inhibited current less than 25% at 100 μM.
DIDS (4,4‐diisothiocyanato‐stilbene‐2,2′disulphonate) inhibited VSOR Cl− current more potently than SITS (4‐acetamido‐4′‐isothiocyanato‐stilbene‐2,2′‐disulphonate). IC50s were 0.84 and 226 μM, respectively.
VSOR Cl− current was strongly inhibited by tamoxifen ([Z]‐1‐[p‐dimethylaminoethoxy‐phenyl]‐1,2‐diphenyl‐1‐butene), an anti‐oestrogen compound (IC50=0.57 μM).
Gd3+ antagonized VSOR Cl− current more potently than La3+. The IC50 for Gd3+ was 23 μM. In contrast, 100 μM La3+ inhibited current only 35±7%.
Antagonists of VSOR Cl− current had non‐specific effects. These compounds blocked voltage‐dependent K+ and Ca2+ currents in colonic myocytes. Tamoxifen (10 μM) and DIDS (10 μM) inhibited L‐type Ca2+ current 87±7 and 31±5%, respectively. Additionally, in the presence of 300 nM charybdotoxin, tamoxifen (1 μM) and DIDS (10 μM) inhibited delayed rectifier K+ current 38±8 and 10±2%, respectively.
The pharmacology of VSOR Cl− channels overlaps with voltage‐dependent cation channels. DIDS and tamoxifen inhibited VSOR Cl− equally. However, because DIDS had much less effect on L‐type Ca2+ and delayed rectifier K+ channels than did tamoxifen, it might be useful in experiments to investigate the physiological and pathophysiological role of this conductance in whole tissues.
Volume‐Sensitive, Outwardly Rectifying (VSOR) Cl− currents were measured in canine colonic myocytes by whole‐cell patch clamp. Decreasing extracellular osmolarity 50 milliosmoles l−1 activated current that was carried by Cl− and 5–7 times greater in the outward direction.
Niflumic acid, an inhibitor of Ca2+‐activated Cl− channels, did not inhibit VSOR Cl− current. Glibenclamide, an antagonist of CFTR, and anthracene‐9‐carboxylate (9‐AC) inhibited current less than 25% at 100 μM.
DIDS (4,4‐diisothiocyanato‐stilbene‐2,2′disulphonate) inhibited VSOR Cl− current more potently than SITS (4‐acetamido‐4′‐isothiocyanato‐stilbene‐2,2′‐disulphonate). IC50s were 0.84 and 226 μM, respectively.
VSOR Cl− current was strongly inhibited by tamoxifen ([Z]‐1‐[p‐dimethylaminoethoxy‐phenyl]‐1,2‐diphenyl‐1‐butene), an anti‐oestrogen compound (IC50=0.57 μM).
Gd3+ antagonized VSOR Cl− current more potently than La3+. The IC50 for Gd3+ was 23 μM. In contrast, 100 μM La3+ inhibited current only 35±7%.
Antagonists of VSOR Cl− current had non‐specific effects. These compounds blocked voltage‐dependent K+ and Ca2+ currents in colonic myocytes. Tamoxifen (10 μM) and DIDS (10 μM) inhibited L‐type Ca2+ current 87±7 and 31±5%, respectively. Additionally, in the presence of 300 nM charybdotoxin, tamoxifen (1 μM) and DIDS (10 μM) inhibited delayed rectifier K+ current 38±8 and 10±2%, respectively.
The pharmacology of VSOR Cl− channels overlaps with voltage‐dependent cation channels. DIDS and tamoxifen inhibited VSOR Cl− equally. However, because DIDS had much less effect on L‐type Ca2+ and delayed rectifier K+ channels than did tamoxifen, it might be useful in experiments to investigate the physiological and pathophysiological role of this conductance in whole tissues.
British Journal of Pharmacology (1999) 127, 1819–1831; doi:10.1038/sj.bjp.0702730
DOI: 10.1038/sj.bjp.0702730
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