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The Journal of Neuroscience, November 15, 2000, 20(22):8365-8376
Inositol 1,4,5-Trisphosphate (IP3)-Mediated
Ca2+ Release Evoked by Metabotropic Agonists and
Backpropagating Action Potentials in Hippocampal CA1 Pyramidal
Neurons
Takeshi
Nakamura,
Kyoko
Nakamura,
Nechama
Lasser-Ross,
Jean-Gaël
Barbara,
Vladislav M.
Sandler, and
William N.
Ross
Department of Physiology, New York Medical College, Valhalla, New
York 10595
We examined the properties of
[Ca2+]i changes 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) agonists t-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 as
t-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 IP3 receptors are not associated
closely with specific Ca2+ channels and are
not close to each other.
Key words:
pyramidal neuron; dendrite; IP3 receptor; metabotropic receptor; BAPTA; EGTA; carbachol; bis-fura-2; furaptra; endoplasmic reticulum
Copyright © 2000 Society for Neuroscience 0270-6474/00/20228365-12$05.00/0
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