Homer 1a enhances spike-induced calcium influx via L-type calcium channels in neocortex pyramidal cells.
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.
Yamamoto
Kenji
K
Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Sakagami
Yu
Y
Sugiura
Shigeki
S
Inokuchi
Kaoru
K
Shimohama
Shun
S
Kato
Nobuo
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects*; D002352:Carrier Proteins / Q000494:pharmacology*; D004594:Electrophysiology; D004597:Electroshock; D000072233:Homer Scaffolding Proteins; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010783:Photometry; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012640:Seizures / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; D010738:Type C Phospholipases; D002118:Calcium