Homer 1a enhances spike-induced calcium influx via L-type calcium channels in neocortex pyramidal cells

Kenji Yamamoto, Yu Sakagami, Shigeki Sugiura, Kaoru Inokuchi, Shun Shimohama, Nobuo Kato*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The scaffold protein family Homer/Vesl serves to couple surface receptors or channels with endoplasmic calcium release channels. Homer 1a/Vesl-1S is regarded as regulating such coupling in an activity-dependent manner. The present calcium photometry and electrophysiological measurement revealed that Homer 1a up-regulates voltage-dependent calcium channels (VDCCs), depending on inositol-1,4,5-trisphosphate (IP3) receptors (IP3Rs). In rat neocortex pyramidal cells, intracellular injection by diffusion from the patch pipette (referred to as 'infusion') of Homer 1a protein enhanced spike-induced calcium increase, depending on both the protein concentration and spike frequency. Induction of this enhancement was disrupted by blockers of key molecules of the mGluR-IP3 signalling pathway, including metabotropic glutamate receptors (mGluRs), phospholipase C and IP3Rs. However, infusion of IP3 failed to mimic the effect of Homer 1a, suggesting requirement for a second Homer 1a-mediated signalling as well as the mGluR-IP3 signalling. In contrast to the induction, maintenance of this enhancement was independent of the mGluR-IP3 signalling, taking the form of augmented calcium influx via L-type VDCCs. Presumably due to the VDCC up-regulation, threshold currents for calcium spikes were reduced. Given that Homer 1a induction is thought to down-regulate neural excitability and hence somatic spike firing, this facilitation of calcium spikes concomitant with such attenuated firing may well have a critical impact on bi-directional synaptic plasticity.

Original languageEnglish
Pages (from-to)1338-1348
Number of pages11
JournalEuropean Journal of Neuroscience
Volume22
Issue number6
DOIs
StatePublished - 2005/09

Keywords

  • Calcium channels
  • Calcium influx
  • Electroconvulsive shock
  • Glutamate receptor
  • Rat
  • Scaffold protein

ASJC Scopus subject areas

  • General Neuroscience

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