Effects of sulfonamides on a metabolite-regulated ATPi-sensitive K+ channel in rat pancreatic B-cells.
Intracellular ATP (ATPi)-sensitive K+ [K+(ATP)] channels are now a recognized site of action of clinically useful hypoglycemic and hyperglycemic sulfonamides. We have further examined the action of these agents on single K+ channels in rat pancreatic B-cells 1) Tolbutamide and glyburide, two hypoglycemic sulfonylureas which decrease K+(ATP) channel activity in the cell-attached patch, affect the kinetics of K+(ATP) channel in a manner similar to glucose. They shorten the duration of the "burst," or cluster of open channel events, while lengthening the intervals between bursts. 2) The hyperglycemic vasodilator diazoxide increases mean K+(ATP) channel activity in the cell-attached patch as well as in the inside-out excised patch exposed to ATPi. It appears to lengthen channel bursts and shorten the intervals between them. Two structurally similar diuretics, hydrochlorothiazide and furosemide, which have mild hyperglycemic effects, do not increase K+(ATP) channel activity even at clinically toxic concentrations. 3) Neither the sulfonylureas nor diazoxide directly affect the activity of single delayed rectifier K+ channels or single calcium and voltage-activated K+ channels in normal B-cells.
Gillis
K D
KD
Department of Internal Medicine, Washington University, St. Louis, Missouri 63110.
Gee
W M
WM
Hammoud
A
A
McDaniel
M L
ML
Falke
L C
LC
Misler
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D004553:Electric Conductivity; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials; D008954:Models, Biological; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005947:Glucose; D003981:Diazoxide; D005905:Glyburide