Hyperpolarization of hepatocytes by 2,5-anhydro-d-mannitol (2,5
-am): implications for hepatic control of food intake.
Scharrer, Erwin, Rinaldo Rossi, David A. Sutter, Marie-Christine
Seebacher, Sandra Boutellier, and Thomas A. Lutz0.
Institute of Veterinary Physiology, University of Z[umlaut]urich,
CH-8057 Z[umlaut]urich, Switzerland
APStracts 3:0386R, 1996.
Hyperpolarization of hepatocytes by 2,5-anhydro-D-mannitol (2,5-AM):
Implications for hepatic control of food intake. Am. J. Physiol.
(Regulatory Integrative Comp. Physiol.) R000 - R000, 1995. Since 2,5
-AM seems to stimulate feeding by acting on the liver and since the
hepatic membrane potential has been suggested to play an important
role in control of feeding ("potentiostatic" hypothesis),
we investigated the effect of 2,5-AM on the membrane potential of
liver cells with microelectrodes using a superfused liver slice
technique. 2,5-AM (2.5 mmol/l) that reduces intracellular ATP in rat
liver hyperpolarized the liver cell membrane in mouse and rat liver
slices by 4-7 mV. This hyperpolarization was reversed by quinine (1
mmol/l), an unspecific blocker of Ca2+-dependent K+ channels and
abolished by apamin (20 nmol/l), a blocker of Ca2+-activated K+
channels with low conductance. 10-3 mol/l, but not 10-6 mol/l
amiloride or a low Na medium (26 mmol/l) also eliminated the
hyperpolarization. The K+ channel blockers cetiedil (50 [mu]mol/l),
glybenclamide (30 [mu]mol/l) and Ba (5 mmol/l), flufenamic acid (100
[mu]mol/l), a blocker of nonselective cation channels, and ouabain (1
mmol/l), an inhibitor of the Na+, K+-ATPase, did not significantly
influence the 2,5-AM induced hyperpolarization.
Received 14 November 1995; accepted in final form 1 October 1996.
APS Manuscript Number R710-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996