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

Eur J Neurosci. 2005 Sep;22(6):1338-48. doi: 10.1111/j.1460-9568.2005.04278.x.


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.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels, L-Type / drug effects*
  • Calcium Signaling / drug effects*
  • Carrier Proteins / pharmacology*
  • Electrophysiology
  • Electroshock
  • Homer Scaffolding Proteins
  • Male
  • Membrane Potentials / drug effects
  • Neocortex / cytology
  • Neocortex / drug effects
  • Neocortex / metabolism*
  • Patch-Clamp Techniques
  • Photometry
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism
  • Recombinant Proteins / pharmacology
  • Seizures / metabolism
  • Type C Phospholipases / metabolism


  • Calcium Channels, L-Type
  • Carrier Proteins
  • Homer Scaffolding Proteins
  • Receptors, Metabotropic Glutamate
  • Recombinant Proteins
  • Type C Phospholipases
  • Calcium