Effects of anion channel antagonists in canine colonic myocytes: comparative pharmacology of Cl-, Ca2+ and K+ currents

Br J Pharmacol. 1999 Aug;127(8):1819-31. doi: 10.1038/sj.bjp.0702730.


1. 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. 2. 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 microM. 3. 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 microM, respectively. 4. 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 microM). 5. Gd3+ antagonized VSOR Cl- current more potently than La3+. The IC50 for Gd3+ was 23 microM. In contrast, 100 microM La3+ inhibited current only 35+/-7%. 6. Antagonists of VSOR Cl- current had non-specific effects. These compounds blocked voltage-dependent K+ and Ca2+ currents in colonic myocytes. Tamoxifen (10 microM) and DIDS (10 microM) inhibited L-type Ca2+ current 87+/-7 and 31+/-5%, respectively. Additionally, in the presence of 300 nM charybdotoxin, tamoxifen (1 microM) and DIDS (10 microM) inhibited delayed rectifier K+ current 38+/-8 and 10+/-2%, respectively. 7. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology*
  • Animals
  • Antiporters / antagonists & inhibitors*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects*
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / drug effects*
  • Colon / cytology
  • Colon / drug effects*
  • Dogs
  • Female
  • Hypotonic Solutions / pharmacology
  • Isotonic Solutions / pharmacology
  • Male
  • Muscle, Smooth / drug effects
  • Patch-Clamp Techniques
  • Potassium Channel Blockers
  • Potassium Channels / drug effects*


  • Antiporters
  • Calcium Channel Blockers
  • Calcium Channels
  • Chloride Channels
  • Hypotonic Solutions
  • Isotonic Solutions
  • Potassium Channel Blockers
  • Potassium Channels
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid