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J Neurophysiol 96: 1829-1837, 2006. First published June 28, 2006; doi:10.1152/jn.00280.2006
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Kainate Receptor–Mediated Inhibition of Glutamate Release Involves Protein Kinase A in the Mouse Hippocampus

José V. Negrete-Díaz1, Talvinder S. Sihra2, José M. Delgado-García1 and Antonio Rodríguez-Moreno1

1División de Neurociencias, Universidad Pablo de Olavide, Seville, Spain; and 2Department of Pharmacology, University College London, London, United Kingdom

Submitted 15 March 2006; accepted in final form 6 June 2006

The mechanisms involved in the inhibition of glutamate release mediated by the activation of presynaptic kainate receptors (KARs) at the hippocampal mossy fiber–CA3 synapse are not well understood. We have observed a long-lasting inhibition of CA3 evoked excitatory postsynaptic currents (eEPSCs) after a brief application of kainate (KA) at concentrations ranging from 0.3 to 10 µM. The inhibition outlasted the change in holding current caused by the activation of ionotropic KARs in CA3 pyramidal cells, indicating that this action is not contingent on the opening of the receptor channels. The inhibition of the eEPSCs by KA was prevented by G protein and protein kinase A (PKA) inhibitors and was enhanced after stimulation of the adenylyl cyclase (AC) with forskolin. We conclude that KARs present at mossy fiber terminals mediate the inhibition of glutamate release through a metabotropic mechanism that involves the activation of an AC-second messenger cAMP-PKA signaling cascade.

Address for reprint requests and other correspondence: A. Rodríguez-Moreno, Div. de Neurociencias, Univ. Pablo de Olavide, Ctra. de Utrera, Km. 1, 41013 Seville, Spain (E-mail: arodmor{at}upo.es)




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