Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Integrins regulate cytoplasmic calcium levels ([Ca2+]) in various cell types but information on activities in neurons is limited. The issue is of current interest because of the evidence that both integrins and changes in [Ca2+]i are required for Long-Term Potentiation. Accordingly, the present studies evaluated integrin ligand effects in cortical neurons. Integrin ligands or alpha 5 beta 1 integrin activating antisera rapidly increased [Ca2+]i with effects greater in glutamatergic than GABAergic neurons, absent in astroglia, and blocked by 0 1 integrin neutralizing antisera and the tyrosine kinase antagonist genistein. Increases depended upon extracellular calcium and intracellular store release. Ligand-induced effects were reduced by voltage-sensitive calcium channel and NMDA receptor antagonists, but blocked by tetrodotoxin or AMPA receptor antagonists. These results indicate that integrin ligation triggers AMPA receptor/depolarization -dependent calcium influx followed by intracellular store release and suggest the possibility that integrin modulation of activity-induced changes in [Ca2+]i contributes importantly to lasting synaptic plasticity in forebrain neurons. (c) 2008 Elsevier Inc. All rights reserved.