Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons

Charles P. Gilman, Tracy Ann Perry, Katsotoshi Furukawa, Nigel H. Grieg, Josephine M. Egan, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Glucagon-like peptide 1 (GLP-1) activates receptors coupled to cAMP production and calcium influx in pancreatic cells, resulting in enhanced glucose sensitivity and insulin secretion. Despite evidence that the GLP-1 receptor is present and active in neurons, little is known of the roles of GLP-1 in neuronal physiology. As GLP-1 modulates calcium homeostasis in pancreatic beta cells, and because calcium plays important roles in neuronal plasticity and neurodegenerative processes, we examined the effects of GLP-1 on calcium regulation in cultured rat hippocampal neurons. When neurons were pre-treated with GLP-1, calcium responses to glutamate and membrane depolarization were attenuated, Whole-cell patch clamp analyses showed that glutamate-induced currents and currents through voltage-dependent calcium channels were significantly decreased in neurons pretreated with GLP-1. Pre-treatment of neurons with GLP-1 significantly decreased their vulnerability to death induced by glutamate. Acute application of GLP-1 resulted in a transient elevation of intracellular calcium levels, consistent with the established effects of GLP-1 on cAMP production and activation of cAMP response element-binding protein. Collectively, our findings suggest that, by modulating calcium responses to glutamate and membrane depolarization, GLP-1 may play important roles in regulating neuronal plasticity and cell survival.

Original languageEnglish (US)
Pages (from-to)1137-1144
Number of pages8
JournalJournal of Neurochemistry
Volume87
Issue number5
DOIs
StatePublished - Dec 2003

Keywords

  • Calcium channels
  • Cyclic AMP
  • Cyclic AMP response element-binding protein
  • Diabetes
  • Excitotoxicity
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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