Postsynaptic IP3 receptor-mediated Ca2+ release modulates synaptic transmission in hippocampal neurons

Ca2+-dependent mechanisms are important in regulating synaptic transmission. The results herein indicate that whole-cell perfusion of inositol 1,4,5-trisphosphate receptor (IP3R) agonists greatly enhanced excitatory postsynaptic current (EPSC) amplitudes in postsynaptic hippocampal CA1 neurons. IP3R agonist-mediated increases in synaptic transmission changed during development and paralleled age-dependent increases in hippocampal type-1 IP3Rs. IP3R agonist-mediated increases in EPSC amplitudes were inhibited by postsynaptic perfusion of inhibitors of Ca2+/calmodulin, PKC and Ca2+/calmodulin-dependent protein kinase II. Postsynaptic perfusion of inhibitors of smooth endoplasmic reticulum (SER) Ca2+-ATPases, which deplete intracellular Ca2+ stores, also enhanced EPSC amplitudes. Postsynaptic perfusion of the IP3R agonist adenophostin (AdA) during subthreshold stimulation appeared to convert silent to active synapses; synaptic transmission at these active synapses was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Postsynaptic IP3R-mediated Ca2+ release also produced a significant increase in spontaneous EPSC frequency. These results indicate that Ca2+ release from intracellular stores play a key role in regulating the function of postsynaptic AMPARs.