Reversal of glibenclamide- and voltage-block of an epithelial k(
atp) channel.
Mayorga-Wark, O., W. P. Dubinsky, and Stanley G. Schultz.
Department of Integrative Biology, University of Texas Medical
School, Houston, Texas 77030
APStracts 3:0140C, 1996.
Potassium channels present in basolateral membrane vesicles isolated
from Necturus maculosa small intestinal cells and reconstituted into
planar phospholipid bilayers are inhibited by MgATP and sulfonylurea
derivatives, such as tolbutamide and glibenclamide, when these agents
are added to the solution bathing the inner mouth of the channel. In
addition, these channels possess an intrinsic "voltage-gate"
and are blocked when the electrical potential difference across the
channel is oriented so that the inner solution is electrically
positive with respect to the outer solution. We now show that
increasing the concentration of permeant ions such as K+ or Rb+ in
the outer solution reverses channel inhibition resulting from the
addition of 50 [mu]M glibenclamide to the inner solution and also
inhibits intrinsic voltage-gating; these effects are not elicited by
increasing the concentrations of the relatively impermeant ions, Na+
or choline in the outer solution. Further, increasing the K+
concentration in the outer solution in the absence of glibenclamide
inhibits voltage-gating and, under these conditions, the subsequent
addition of glibenclamide to the inner solution is ineffective. These
results are consistent with a model in which the voltage-gate is an
open-channel blocker whose action is directly reversed by elevating
the external concentration of relatively permeant cations and where
the action of glibenclamide is to stabilize the inactivated state of
the channel possibly through hydrophobic interactions.
Received 8 September 1995; accepted in final form 12 April 1996.
APS Manuscript Number C549-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96