Inhibition of KATP channel activity by troglitazone in CRI-G1 insulin-secreting cells.
Patch-clamp recording techniques were used to examine the effect of troglitazone on KATP channel activity in Cambridge rat insulinoma-G1 (CRI-G1) insulin-secreting cells. In both inside-out and outside-out patch recordings, bath application of troglitazone reduced KATP channel activity. This inhibition was independent of the membrane voltage and was poorly reversible. In whole-cell studies, troglitazone inhibited KATP channel currents with an IC50 of 697 +/- 92 nM and an associated Hill coefficient of 1.2 +/- 0.2. In current clamp recordings 10 microM troglitazone depolarised the CRI-G1 cell membrane by 36.8 +/- 3.9 mV with a concomitant decrease in membrane conductance. However, in contrast to the rapid depolarisation produced by tolbutamide, the effects of troglitazone developed more slowly, usually taking 15-20 min to develop.
Parke Daris Neuroscience Research Centre, Cambridge University Forvie Site, UK.
K
K
Lee
T
T
Ibbotson
P J
PJ
Richardson
P R
PR
Boden
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014044:Tolbutamide; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D026902:Potassium Channel Blockers; D013844:Thiazoles; D045162:Thiazolidinediones; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D000077288:Troglitazone