TY - JOUR
T1 - Effects of anion channel antagonists in canine colonic myocytes
T2 - Comparative pharmacology of Cl-, Ca2+ and K+ currents
AU - Dick, Gregory M.
AU - Kong, In Deok
AU - Sanders, Kenton M.
PY - 1999
Y1 - 1999
N2 - 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 μM. 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 μM, 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 μM). 5. 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%. 6. 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. 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.
AB - 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 μM. 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 μM, 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 μM). 5. 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%. 6. 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. 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.
KW - DIDS
KW - Delayed rectifier K channels
KW - Smooth muscle
KW - Tamoxifen
KW - Voltage-gated Ca channels
KW - Volume-sensitive Cl channels
UR - http://www.scopus.com/inward/record.url?scp=0032791988&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0702730
DO - 10.1038/sj.bjp.0702730
M3 - Article
C2 - 10482912
AN - SCOPUS:0032791988
SN - 0007-1188
VL - 127
SP - 1819
EP - 1831
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 8
ER -