Modulation of AMPA receptor-mediated ion current by pituitary adenylate cyclase-activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus. Export

@article{citeulike:3179775, abstract = {Pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotrophic and neuromodulatory peptide, was recently shown to enhance NMDA receptor-mediated currents in the hippocampus (Macdonald, et al. 2005. J Neurosci 25:11374-11384). To check if PACAP might also modulate AMPA receptor function, we tested its effects on AMPA receptor-mediated synaptic currents on CA1 pyramidal neurons, using the patch clamp technique on hippocampal slices. In the presence of the NMDA antagonist D-AP5, PACAP (10 nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of Schaffer collaterals. Following a paired-pulse stimulation protocol, the paired-pulse ratio was unaffected in most neurons, suggesting that the AMPA-mediated EPSC was modulated by PACAP mainly at a postsynaptic level. PACAP also modulated the currents induced on CA1 pyramidal neurons by applications of either glutamate or AMPA. The effects of PACAP were dose-dependent: at a 0.5 nM dose, PACAP increased AMPA-mediated current; such effect was blocked by PACAP 6-38, a selective antagonist of PAC1 receptors. The enhancement of AMPA-mediated current by PACAP 0.5 nM was abolished when cAMPS-Rp, a PKA inhibitor, was added to the intracellular solution. At a 10 nM concentration, PACAP reduced AMPA-mediated current; such effect was not blocked by PACAP 6-38. The inhibitory effect of 10 nM PACAP was mimicked by Bay 55-9837 (a selective agonist of VPAC2 receptors), persisted in the presence of intracellular BAPTA and was abolished by intracellular cAMPS-Rp. Stimulation-evoked EPSCs in CA1 neurons were significantly reduced following application of the PAC1 antagonist PACAP 6-38; this result indicates that PAC1 receptors in the CA1 region are tonically activated by endogenous PACAP and enhance CA3-CA1 synaptic transmission. Our results show that PACAP differentially modulates AMPA receptor-mediated current in CA1 pyramidal neurons by activation of PAC1 and VPAC2 receptors, both involving the cAMP/PKA pathway; the functional significance will be discussed in light of the multiple effects exerted by PACAP on the CA3-CA1 synapse at different levels. (c) 2008 Wiley-Liss, Inc.}, address = {Dipartimento di Scienze Fisiologiche, Universit\`{a} di Catania, Viale Andrea Doria 6, 95125 Catania, Italy.}, author = {Costa, L and Santangelo, F and Li Volsi, G and Ciranna, L}, citeulike-article-id = {3179775}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/hipo.20488}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18727050}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18727050}, day = {25}, doi = {10.1002/hipo.20488}, issn = {1098-1063}, journal = {Hippocampus}, keywords = {hippocampus, pacap}, month = {August}, posted-at = {2008-09-01 19:59:11}, priority = {2}, title = {Modulation of AMPA receptor-mediated ion current by pituitary adenylate cyclase-activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus.}, url = {http://dx.doi.org/10.1002/hipo.20488}, year = {2008} }

TY - JOUR ID - citeulike:3179775 L3 - citeulike-article-id:3179775 N2 - Pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotrophic and neuromodulatory peptide, was recently shown to enhance NMDA receptor-mediated currents in the hippocampus (Macdonald, et al. 2005. J Neurosci 25:11374-11384). To check if PACAP might also modulate AMPA receptor function, we tested its effects on AMPA receptor-mediated synaptic currents on CA1 pyramidal neurons, using the patch clamp technique on hippocampal slices. In the presence of the NMDA antagonist D-AP5, PACAP (10 nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked in CA1 pyramidal neurons by stimulation of Schaffer collaterals. Following a paired-pulse stimulation protocol, the paired-pulse ratio was unaffected in most neurons, suggesting that the AMPA-mediated EPSC was modulated by PACAP mainly at a postsynaptic level. PACAP also modulated the currents induced on CA1 pyramidal neurons by applications of either glutamate or AMPA. The effects of PACAP were dose-dependent: at a 0.5 nM dose, PACAP increased AMPA-mediated current; such effect was blocked by PACAP 6-38, a selective antagonist of PAC1 receptors. The enhancement of AMPA-mediated current by PACAP 0.5 nM was abolished when cAMPS-Rp, a PKA inhibitor, was added to the intracellular solution. At a 10 nM concentration, PACAP reduced AMPA-mediated current; such effect was not blocked by PACAP 6-38. The inhibitory effect of 10 nM PACAP was mimicked by Bay 55-9837 (a selective agonist of VPAC2 receptors), persisted in the presence of intracellular BAPTA and was abolished by intracellular cAMPS-Rp. Stimulation-evoked EPSCs in CA1 neurons were significantly reduced following application of the PAC1 antagonist PACAP 6-38; this result indicates that PAC1 receptors in the CA1 region are tonically activated by endogenous PACAP and enhance CA3-CA1 synaptic transmission. Our results show that PACAP differentially modulates AMPA receptor-mediated current in CA1 pyramidal neurons by activation of PAC1 and VPAC2 receptors, both involving the cAMP/PKA pathway; the functional significance will be discussed in light of the multiple effects exerted by PACAP on the CA3-CA1 synapse at different levels. (c) 2008 Wiley-Liss, Inc. JF - Hippocampus SN - 1098-1063 AD - Dipartimento di Scienze Fisiologiche, Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy. TI - Modulation of AMPA receptor-mediated ion current by pituitary adenylate cyclase-activating polypeptide (PACAP) in CA1 pyramidal neurons from rat hippocampus. KW - hippocampus KW - pacap AU - Costa, L AU - Santangelo, F AU - Li Volsi, G AU - Ciranna, L PY - 2008/08/25/ UR - http://dx.doi.org/10.1002/hipo.20488 ER -