Inositol 1,4,5-Trisphosphate (IP3)-Mediated Ca2+Release Evoked by Metabotropic Agonists and Backpropagating Action Potentials in Hippocampal CA1 Pyramidal Neurons

Open Access
Publisher Website
Google Scholar
Abstract
We examined the properties of [Ca2+]ichanges that were evoked by backpropagating action potentials in pyramidal neurons in hippocampal slices from the rat. In the presence of the metabotropic glutamate receptor (mGluR) agonistst-ACPD, DHPG, or CHPG, spikes caused Ca2+waves that initiated in the proximal apical dendrites and spread over this region and in the soma. Consistent with previously described synaptic responses (Nakamura et al., 1999a), pharmacological experiments established that the waves were attributable to Ca2+release from internal stores mediated by the synergistic effect of receptor-mobilized inositol 1,4,5-trisphosphate (IP3) and spike-evoked Ca2+. The amplitude of the changes reached several micromoles per liter when detected with the low-affinity indicators fura-6F, fura-2-FF, or furaptra. Repetitive brief spike trains at 30–60 sec intervals generated increases of constant amplitude. However, trains at intervals of 10–20 sec evoked smaller increases, suggesting that the stores take 20–30 sec to refill. Release evoked by mGluR agonists was blocked by MCPG, AIDA, 4-CPG, MPEP, and LY367385, a profile consistent with the primacy of group I receptors. At threshold agonist concentrations the release was evoked only in the dendrites; threshold antagonist concentrations were effective only in the soma. Carbachol and 5-HT evoked release with the same spatial distribution ast-ACPD, suggesting that the distribution of neurotransmitter receptors was not responsible for the restricted range of regenerative release. Intracellular BAPTA and EGTA were approximately equally effective in blocking release. Extracellular Cd2+blocked release, but no single selective Ca2+channel blocker prevented release. These results suggest that IP3receptors are not associated closely with specific Ca2+channels and are not close to each other.