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Volume 17, Number 11, Issue of June 1, 1997 pp. 4129-4135
Copyright ©1997 Society for Neuroscience

Control of Action Potential-Induced Ca²⁺ Signaling in the Soma of Hippocampal Neurons by Ca²⁺ Release from Intracellular Stores

Received Jan. 31, 1997; revised March 4, 1997; accepted March 5, 1997.

Jason M. Jacobs and Tobias Meyer

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710

Stimulus-induced increases in neuronal Ca²⁺ concentration are important signaling events for transcriptional regulation and neuronal plasticity. Electrical inputs are thought to mediate Ca²⁺ responses in the soma by triggering action potentials, which in turn open voltage-gated Ca²⁺ channels in the somatic plasma membrane. It is not yet known to what extent internal Ca²⁺ amplification contributes to the somatic Ca²⁺ responses. Here we used fluorescent Ca²⁺ measurements in cultured hippocampal neurons and report that the amplitude of the somatic Ca²⁺ increase triggered by field stimulation is independent of the extracellular Ca²⁺ concentration as long as the concentration is greater than 50 µM. Furthermore, significantly more La³⁺ has to be added extracellularly for blocking Ca²⁺ responses, as predicted from the reported La³⁺ dependence of voltage-gated Ca²⁺ channels. These measurements suggest that field stimulation-induced somatic Ca²⁺ responses in hippocampal neurons are largely attributable to Ca²⁺ release from intracellular stores. Only a small number of Ca²⁺ ions have to enter across the plasma membrane for this intracellular Ca²⁺ amplification process to occur. Rapid fluorescence-imaging measurements showed that the internal Ca²⁺ amplification occurs over 10-15 msec and linearly increases intracellular Ca²⁺ concentrations for up to 40 action potentials. At a fixed number of field pulses, frequencies of 40 Hz were optimal for somatic Ca²⁺ increases. Our studies suggest that the opening of intracellular Ca²⁺ release channels plays a crucial part in shaping the action potential-induced neuronal Ca²⁺ response.

Key words: hippocampal neurons; action potential; calcium release; field stimulation; Fluo3; calcium amplification

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