Modulation of calcium current, intracellular calcium levels and cell survival by glucose deprivation and growth factors in hippocampal neurons

Bin Cheng, Douglas G. McMahon, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) can protect CNS neurons against ischemic/excitotoxic insults, but the mechanism of action is unknown. Imaging of the calcium indicator dye fura-3 and whole-cell patch clamp recordings of calcium currents were used to examine the mechanisms whereby hypoglycemia damages and growth factors protect cultured rat hippocampal neurons. When cultures were deprived of glucose, massive neuronal death occured 16-24 h following the onset of hypoglycemia. Early hypoglycemia-induced changes included calcium current inhibition and a reduction in intracellular free calcium levels ([Ca2+]i) without morphological signs of neuronal damage. Later changes included a large elevation of [Ca2+]i which was causally involved in neuronal damage. NGF and bFGF prevented or reduced both early and later responses to hypoglycemia. The growth factors increased calcium (barium) current and [Ca2+]i to normal limits during the early stages of hypoglycemia and prevented the later elevation in [Ca2+]i and neuronal damage. Nifedipine, but not omega-conotoxin, blocked calcium currents. The increased calcium current caused by the growth factors was apparently not sufficient to protect neurons against hypoglycemic damage since K+ depolarization during the early stages of hypoglycemia did not prevent and, in fact exacerbated, the subsequent neuronal damage. In addition, exposure of neurons to K+, NGF or bFGF only during the first 1 h of hypoglycemia did not protect against hypoglycemic damage. Taken together, the data suggest that neurons initially respond to hypoglycemia with a reduction in calcium currents which may provide a means to maintain [Ca2+]i within a concentration range conducive to cell survival. Prolonged energy deprivation eventually results in a failure of calcium extrusion systems, glutamate receptor activation and a loss of neuronal calcium homeostasis. Taken together, the data indicate that the mechanism of growth factor protection against energydeprivation involves of the late prevention rise in [Ca2+]i.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalBrain Research
Volume607
Issue number1-2
DOIs
StatePublished - Apr 2 1993
Externally publishedYes

Fingerprint

Cell Survival
Intercellular Signaling Peptides and Proteins
Hypoglycemia
Calcium
Neurons
Glucose
Nerve Growth Factor
Fibroblast Growth Factor 2
Hypoglycemic Agents
omega-Conotoxins
Glutamate Receptors
Barium
Nifedipine
Homeostasis
Coloring Agents

Keywords

  • Calcium
  • Excitoxicity
  • Fibroblast growth factor
  • Hypoglycemia
  • Nerve growth factor
  • Neuron death
  • Nifedipine
  • Patch clamp

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Modulation of calcium current, intracellular calcium levels and cell survival by glucose deprivation and growth factors in hippocampal neurons. / Cheng, Bin; McMahon, Douglas G.; Mattson, Mark P.

In: Brain Research, Vol. 607, No. 1-2, 02.04.1993, p. 275-285.

Research output: Contribution to journalArticle

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