Metabotropic glutamate receptor activation induces calcium waves within hippocampal dendrites.
1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+]i were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [Ca2+]i were visualized as changes in the fluorescence of the Ca(2+)-sensitive dye Fluo-3. 2. Brief application of the specific mGlu receptor agonist (1S,3R)-ACPD to either the apical or basal dendrites produced initially localized increases in [Ca2+]i that subsequently propagated as waves throughout much of the neuron. These Ca2+ waves, which propagated at approximately 40 microns/s, were shown not to reflect intracellular Ca2+ diffusion or extracellular diffusion of ACPD and were always accompanied by small outward membrane currents. 3. Repetitive application of ACPD failed to trigger further Ca2+ release. We found that a threshold level of voltage-gated Ca2+ entry during trains of action potentials was needed to prime further mGlu-stimulated Ca2+ release. In contrast, the passage of time alone did not cause the mGlu-release system to reactivate--restoration of ACPD-stimulated Ca2+ release. The spike-mediated Ca2+ signal was unaffected by mGlu-stimulated depletion of intracellular stores. 4. These experiments demonstrate that specific mGlu receptor activation can mobilize Ca2+ in dendrites of CA1 neurons and trigger waves of Ca(2+)-induced Ca(2+)-release throughout the cell. A use-dependent relationship between voltage-gated Ca2+ entry during trains of action potentials and mGlu-stimulated Ca2+ release is suggested.
Department of Psychology, Yale University, New Haven, Connecticut 06520-8205.
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Jaffe
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Brown
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D046508:Culture Techniques; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D015220:Calcium Channels; D018094:Receptors, Metabotropic Glutamate; D002118:Calcium