Calcium store depletion induces persistent perisomatic increases in the functional density of h channels in hippocampal pyramidal neurons

Neuron. 2010 Dec 9;68(5):921-35. doi: 10.1016/j.neuron.2010.11.033.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / metabolism
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic Nucleotide-Gated Cation Channels / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Male
  • Potassium Channels / metabolism*
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Second Messenger Systems / physiology
  • Signal Transduction / physiology

Substances

  • Calcium Channels
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Potassium Channels
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium