GLUCOSE-INDUCED INTRACELLULAR ION CHANGES IN SUGAR-SENSITIVE HYPOTHALAMIC
NEURONS.
Ian A Silver and Maria Erecindba.
Department of Anatomy, School of Veterinary Science, University of Bristol,
Bristol BS2 8EJ, UK and +Department of Pharmacology, University of
Pennsylvania, Philadelphia, PA 19104, USA.
APStracts 4:364N, 1997.
ABSTRACT
In the Lateral Hypothalamic Area (LHA) of rat brain about 30% of cells showed
sensitivity to small changes in local concentrations of glucose. These
'glucose-sensitive' neurons demonstrated 4 types of behavior, 3 of which
probably represent segments of a continuous spectrum of recruitment in
response to ever more severe changes in blood sugar. Type I cells showed
maximum activity at and below 5.6 mM blood glucose but became completely
silent at hyperglycemia of 10-12 mM (normoglycemia 7.6 ñ 0.3 mM). Type II and
III neurons exhibited a wider range of response. Type IV cells (5-7% of
glucose sensitive neurons) paralleled the behavior of sugar sensitive cells in
Ventromedial Hypothalamic Nucleus (VMH). In VMH about 40% of cells responded
to changes in blood glucose over a range of concentrations from 3.6 - 17 mM,
by increasing their firing rate as sugar level rose and vice versa. Ionic
shifts during increases in blood (brain) glucose levels were similar in LHA
types I-III but fastest in I and slowest in III. [Na+]i fell by 5-9 mM, [K+]i
rose by 6-8 mM and plasma membrane hyperpolarized by 5 mV. [Ca2+]i declined by
15-20 nM in line with membrane hyperpolarization. In VMH and type IV LHA cells
[K+]i fell 3-8 mM and plasma membrane depolarized -3 to -5 mV as blood/brain
glucose concentration increased from 7.6/2.4 mM to 17.6/4.2 mM while [Ca2+]i
increased from 125 nM to 180 nM as a consequence of falling membrane
potential. During falls in blood/brain sugar concentration the effects in both
VMH and LHA cells were reversed. The findings are consistent with the ionic
shifts in Types I-III LHA cells being dependent on alterations in Na/K-ATPase
activity while those in VMH and Type IV LHA cells could be caused by
modulation of ATP-dependent K+-channels. A possible mechanism for linking the
effects of small changes in glucose to ATP generation which could bring about
the above phenomena, is the interposition of a 'glucokinase-type' enzyme in a
role similar to that which it has in glucose-sensing pancreatic á-cells.
Received 19 June 1995; accepted in final form 3 December 1997.
APS Manuscript Number J392-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997