Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons
Article first published online: 29 OCT 2003
Journal of Neurochemistry
Volume 87, Issue 5, pages 1137–1144, December 2003
How to Cite
Gilman, C. P., Perry, T., Furukawa, K., Grieg, N. H., Egan, J. M. and Mattson, M. P. (2003), Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons. Journal of Neurochemistry, 87: 1137–1144. doi: 10.1046/j.1471-4159.2003.02073.x
- Issue published online: 29 OCT 2003
- Article first published online: 29 OCT 2003
- Received July 2, 2003; revised manuscript received August 6, 2003; accepted August 11, 2003.
- calcium channels;
- cyclic AMP;
- cyclic AMP response element-binding protein;
- synaptic plasticity
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 pre-treated 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.