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 4:0330N, 1997.
ABSTRACT
1. In 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 and 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). 2. 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.
3. 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. 4. 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. 5. During falls in blood/brain sugar concentration the
effects in both VMH and LHA cells were reversed. 6. The findings are
consistent with the ionic shifts in Types I-III LHA cells being dependent on
alterations in the 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 on 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 1997; accepted in final form 18 November 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