Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+ current

Dipayan Chaudhuri, Badr A. Alseikhan, Siao Yun Chang, Tuck Wah Soong, David T. Yue

Research output: Contribution to journalArticlepeer-review

Abstract

P-type (Cav2.1) Ca2+ channels are a central conduit of neuronal Ca2+ entry, so their Ca2+ feedback regulation promises widespread neurobiological impact. Heterologous expression of recombinant Cav2.1 channels demonstrates that the Ca2+ sensor calmodulin can trigger Ca2+-dependent facilitation (CDF) of channel opening. This facilitation occurs when local Ca2+ influx through individual channels selectively activates the C-terminal lobe of calmodulin. In neurons, however, such calmodulin-mediated processes have yet to be detected, and CDF of native P-type current has thus far appeared different, arguably triggered by other Ca2+ sensing molecules. Here, in cerebellar Purkinje somata abundant with prototypic P-type channels, we find that the C-terminal lobe of calmodulin does produce CDF, and such facilitation augments Ca2+ entry during stimulation by repetitive action-potential and complex-spike waveforms. Beyond recapitulating key features of recombinant channels, these neurons exhibit an additional modulatory dimension: developmental upregulation of CDF during postnatal week 2. This phenomenon reflects increasing somatic expression of Cav2.1 splice variants that manifest CDF and progressive dendritic targeting of variants lacking CDF. Calmodulin-triggered facilitation is thus fundamental to native Ca v2.1 and rapidly enhanced during early development.

Original languageEnglish (US)
Pages (from-to)8282-8294
Number of pages13
JournalJournal of Neuroscience
Volume25
Issue number36
DOIs
StatePublished - Sep 7 2005

Keywords

  • Alternative splicing
  • Cerebellar Purkinje neuron
  • EF hand
  • P/Q-type channel
  • Short-term synaptic plasticity
  • α1A

ASJC Scopus subject areas

  • Neuroscience(all)

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