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Influence of Severe Hypoglycemia on Brain Extracellular Calcium and Potassium Activities, Energy, and Phospholipid Metabolism

Wieloch, Tadeusz LU ; Harris, Robert J. ; Symon, Lindsay and Siesjö, Bo K. LU (1984) In Journal of Neurochemistry 43(1). p.160-168
Abstract

Abstract: In the cerebral cortices of rats, during insulininduced hypoglycemia, changes in the concentrations of labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)] and glycolytic metabolites (lactate, pyruvate, and glucose) as well as phospholipids and free fatty acids (FFAs) were studied in relation to extracellular potassium and calcium activities. Changes in extracellular calcium and potassium activities occurred at approximately the onset of isoelectricity. The extracellular calcium activity dropped from 1.17 ± 0.14 mM to 0.18 ± 0.28 mM and the potassium activity rose from 3.4 ± 0.94 mM to 48 ± 12 mM (means ± SD). Minutes prior to this ionic change the levels of ATP, PCr, and phospholipids were unchanged while... (More)

Abstract: In the cerebral cortices of rats, during insulininduced hypoglycemia, changes in the concentrations of labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)] and glycolytic metabolites (lactate, pyruvate, and glucose) as well as phospholipids and free fatty acids (FFAs) were studied in relation to extracellular potassium and calcium activities. Changes in extracellular calcium and potassium activities occurred at approximately the onset of isoelectricity. The extracellular calcium activity dropped from 1.17 ± 0.14 mM to 0.18 ± 0.28 mM and the potassium activity rose from 3.4 ± 0.94 mM to 48 ± 12 mM (means ± SD). Minutes prior to this ionic change the levels of ATP, PCr, and phospholipids were unchanged while the levels of FFAs remained unchanged or slightly elevated. Following the first ionic change the steady‐state levels of ATP decreased by 40%, from 2.42 to 1.56 μmol/g. PCr levels decreased by 75%, from 4.58 to 1.26 μmol/g. Simultaneously, the levels of FFAs increased from 338 to 642 nmol/g, arachidonic acid displaying the largest relative increase, 33 to 130 nmol/g. The first ionic change was followed by a short period of normalization of ionic concentrations followed by a sustained ionic change. This was accompanied by a small additional decrease in ATP (to 1.26 μmol/g). The FEA levels increased to 704 nmol/g. There was a highly sig nificant negative correlation between the levels of FFAs and the energy charge of the tissue. The formation of FFAs was accompanied by a decrease in the phospholipid pool. The largest relative decrease was observed in the inositol phosphoglycerides, followed by serine and ethanolamine phosphoglycerides. After 10 min of isoelectricity the levels of phospholipids had decreased by 5.12 μmol/g while the levels of FFAs had increased by 0.46 μmol/g, indicating oxidative metabolism or washout of the released FFAs. The attenuation of the rapid initial changes in the levels of the energy metabolites and FFAs as well as the correlation between the energy charge and the levels of FFAs suggests that a new steady state is established following the first ionic change. The importance of these reactions for the development of hypogiycemic neuronal damage is discussed.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Calcium, Energy metabolism, Free fatty acids, Hypoglycemia, Phospholipid metabolism, Potassium
in
Journal of Neurochemistry
volume
43
issue
1
pages
160 - 168
publisher
Wiley-Blackwell
external identifiers
  • scopus:0021273322
  • pmid:6726243
ISSN
0022-3042
DOI
10.1111/j.1471-4159.1984.tb06692.x
language
English
LU publication?
yes
id
8b2cddb2-e556-42ac-a6d5-921374b2d23a
date added to LUP
2019-06-13 17:25:07
date last changed
2019-11-25 09:31:33
@article{8b2cddb2-e556-42ac-a6d5-921374b2d23a,
  abstract     = {<p>Abstract:  In the cerebral cortices of rats, during insulininduced hypoglycemia, changes in the concentrations of labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)] and glycolytic metabolites (lactate, pyruvate, and glucose) as well as phospholipids and free fatty acids (FFAs) were studied in relation to extracellular potassium and calcium activities. Changes in extracellular calcium and potassium activities occurred at approximately the onset of isoelectricity. The extracellular calcium activity dropped from 1.17 ± 0.14 mM to 0.18 ± 0.28 mM and the potassium activity rose from 3.4 ± 0.94 mM to 48 ± 12 mM (means ± SD). Minutes prior to this ionic change the levels of ATP, PCr, and phospholipids were unchanged while the levels of FFAs remained unchanged or slightly elevated. Following the first ionic change the steady‐state levels of ATP decreased by 40%, from 2.42 to 1.56 μmol/g. PCr levels decreased by 75%, from 4.58 to 1.26 μmol/g. Simultaneously, the levels of FFAs increased from 338 to 642 nmol/g, arachidonic acid displaying the largest relative increase, 33 to 130 nmol/g. The first ionic change was followed by a short period of normalization of ionic concentrations followed by a sustained ionic change. This was accompanied by a small additional decrease in ATP (to 1.26 μmol/g). The FEA levels increased to 704 nmol/g. There was a highly sig nificant negative correlation between the levels of FFAs and the energy charge of the tissue. The formation of FFAs was accompanied by a decrease in the phospholipid pool. The largest relative decrease was observed in the inositol phosphoglycerides, followed by serine and ethanolamine phosphoglycerides. After 10 min of isoelectricity the levels of phospholipids had decreased by 5.12 μmol/g while the levels of FFAs had increased by 0.46 μmol/g, indicating oxidative metabolism or washout of the released FFAs. The attenuation of the rapid initial changes in the levels of the energy metabolites and FFAs as well as the correlation between the energy charge and the levels of FFAs suggests that a new steady state is established following the first ionic change. The importance of these reactions for the development of hypogiycemic neuronal damage is discussed.</p>},
  author       = {Wieloch, Tadeusz and Harris, Robert J. and Symon, Lindsay and Siesjö, Bo K.},
  issn         = {0022-3042},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {160--168},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Influence of Severe Hypoglycemia on Brain Extracellular Calcium and Potassium Activities, Energy, and Phospholipid Metabolism},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.1984.tb06692.x},
  doi          = {10.1111/j.1471-4159.1984.tb06692.x},
  volume       = {43},
  year         = {1984},
}