Reduced glutathione inhibits beta-NAD+-activated non-selective cation currents in the CRI-G1 rat insulin-secreting cell line.
1. Whole-cell voltage-clamp recordings were used to study the characteristics of a non-selective cation current, activated by intracellular beta-NAD+, present in CRI-G1 insulin-secreting cells. The monovalent cations Na+, K+ and Cs+ were equally permeant through this channel. 2. The magnitude of the beta-NAD+ current was dependent on the concentration of both beta-NAD+ and Ca2+ in the cell. The properties of the beta-NAD+-activated macroscopic current are similar to those of the beta-NAD+-activated non-selective cation channel (NSNAD) examined at the single channel level in this cell line. 3. The presence of intracellular reduced glutathione (GSH) inhibited the beta-NAD+-activated macroscopic current and the activity of the NSNAD channel in inside-out patch recordings. 4. The inhibition of beta-NAD+-activated currents by GSH is mimicked by its analogue ophthalmic acid but not by another thiol reducing agent dithiothreitol, indicating the presence of a specific GSH binding site present on the NSNAD channel or associated protein.
Herson
P S
PS
Department of Biomedical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD,, UK.
Ashford
M L
ML
D000818:Animals; D002412:Cations / Q000378:metabolism; D002460:Cell Line; D002586:Cesium / Q000493:pharmacokinetics; D005978:Glutathione / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000187:drug effects*; D009243:NAD / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology
D002412:Cations; D007004:Hypoglycemic Agents; D007328:Insulin; D009842:Oligopeptides; D009243:NAD; D002586:Cesium; C016632:ophthalmic acid; D014044:Tolbutamide; D005978:Glutathione