Neuron
Volume 68, Issue 5, 9 December 2010, Pages 921-935
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Article
Calcium Store Depletion Induces Persistent Perisomatic Increases in the Functional Density of h Channels in Hippocampal Pyramidal Neurons

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Summary

The regulation of intracellular calcium by the endoplasmic reticulum (ER) plays a critical role in neuronal function. While the consequences associated with depleting calcium from the ER have been studied in multiple systems, it is not known whether the intrinsic properties of a neuron change in response to such perturbations. In this study, we demonstrate that the depletion of calcium from the ER of hippocampal CA1 pyramidal neurons induces a persistent, perisomatic increase in the density of functional h channels resulting in a reduction in intrinsic excitability and an increase in the optimal response frequency. This form of intrinsic plasticity is dependent on the elevation of cytoplasmic calcium, inositol triphosphate receptors, store-operated calcium channels, and the protein kinase A pathway. We postulate that this form of depletion-induced intrinsic plasticity is a neuroprotective mechanism that reduces excitability after depletion of calcium stores triggered through altered network activity during pathological conditions.

Highlights

► Depletion of ER calcium stores increases functional density of h channels ► Depletion-induced plasticity of intrinsic dynamics and excitability are perisomatic ► Depletion-induced intrinsic plasticity is dependent on InsP3 receptors + SOC channels ► Depletion-induced intrinsic plasticity is dependent on the PKA pathway

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Present address: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India