Erbin enhances voltage-dependent facilitation of Cav1.3 Ca 2+ channels through relief of an autoinhibitory domain in the Ca v1.3 α1 subunit

Irina Calin-Jageman, Kuai Yu, Randy A. Hall, Lin Mei, Amy Lee

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Cav1.3 (L-type) voltage-gated Ca2+ channels have emerged as key players controlling Ca2+ signals at excitatory synapses. Compared with the more widely expressed Cav1.2 L-type channel, relatively little is known about the mechanisms that regulate Ca v1.3 channels. Here, we describe a new role for the PSD-95 (postsynaptic density-95)/Discs large/ZO-1 (zona occludens-1) (PDZ) domain-containing protein, erbin, in directly potentiating Cav1.3. Erbin specifically forms a complex with Cav1.3, but not Ca v1.2, in transfected cells. The significance of erbin/Ca v1.3 interactions is supported by colocalization in somatodendritic domains of cortical neurons in culture and coimmunoprecipitation from rat brain lysates. In electrophysiological recordings, erbin augments facilitation of Cav1.3 currents by a conditioning prepulse, a process known as voltage-dependent facilitation (VDF). This effect requires a direct interaction of the erbin PDZ domain with a PDZ recognition site in the C-terminal domain (CT) of the long variant of the Cav1.3 α1 subunit (α11.3). Compared with Cav1.3, the Ca v1.3b splice variant, which lacks a large fraction of the α11.3 CT, shows robust VDF that is not further affected by erbin. When coexpressed as an independent entity with Cav1.3b or Cav1.3 plus erbin, the α11.3 CT strongly suppresses VDF, signifying an autoinhibitory function of this part of the channel. These modulatory effects of erbin, but not α11.3 CT, depend on the identity of the auxiliary Ca2+ channel β subunit. Our findings reveal a novel mechanism by which PDZ interactions and alternative splicing of α11.3 may influence activity-dependent regulation of Ca v1.3 channels at the synapse.

Original languageEnglish (US)
Pages (from-to)1374-1385
Number of pages12
JournalJournal of Neuroscience
Volume27
Issue number6
DOIs
Publication statusPublished - Feb 7 2007

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Keywords

  • Excitability
  • Facilitation
  • L-type
  • PDZ domain
  • Plasticity
  • Voltage-gated Ca channel

ASJC Scopus subject areas

  • Neuroscience(all)

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