AJP - Cell Physiology, Vol 257, Issue 6 C1119-C1127, Copyright © 1989 by American Physiological Society
Effects of sulfonamides on a metabolite-regulated ATPi-sensitive K+ channel in rat pancreatic B-cells
K. D. Gillis, W. M. Gee, A. Hammoud, M. L. McDaniel, L. C. Falke and S. Misler
Department of Internal Medicine, Washington University, St. Louis, Missouri 63110.
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.
