Alternative splicing as a molecular switch for Ca2+/calmodulin- dependent facilitation of P/Q-type Ca2+ channels

Dipayan Chaudhuri, Siao Yun Chang, Carla D. DeMaria, Rebecca S. Alvania, Tuck Wah Soong, David T. Yue

Research output: Contribution to journalArticle

Abstract

Alternative splicing of the P/Q-type channel (Cav2.1) promises customization of the computational repertoire of neurons. Here we report that concerted splicing of its main α1A subunit, at both an EF-hand-like domain and the channel C terminus, controls the form of Ca 2+-dependent facilitation (CDF), an activity-dependent enhancement of channel opening that is triggered by calmodulin. In recombinant channels, such alternative splicing switches CDF among three modes: (1) completely "ON" and driven by local Ca2+ influx through individual channels, (2) completely "OFF," and (3) partially OFF but inducible by elevated global Ca2+ influx. Conversion from modes 1 to 3 represents an unprecedented dimension of control. The physiological function of these variants is likely important, because we find that the distribution of EF-hand splice variants is strikingly heterogeneous in the human brain, varying both across regions and during development.

Original languageEnglish (US)
Pages (from-to)6334-6342
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number28
DOIs
StatePublished - Jul 14 2004

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Keywords

  • Ca -dependent inactivation
  • Ca2.1
  • Developmental alternative splicing
  • EF hand
  • Exon 37
  • Short-term synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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