Transmitter modulation of slow, activity-dependent alterations in sodium channel availability endows neurons with a novel form of cellular plasticity

David B. Carr, Michelle Day, Angela R. Cantrell, Joshua Held, Todd Scheuer, William A. Catterall, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

Voltage-gated Na+ channels are major targets of G protein-coupled receptor (GPCR)-initiated signaling cascades. These cascades act principally through protein kinase-mediated phosphorylation of the channel α subunit. Phosphorylation reduces Na+ channel availability in most instances without producing major alterations of fast channel gating. The nature of this change in availability is poorly understood. The results described here show that both GPCR- and protein kinase-dependent reductions in Na+ channel availability are mediated by a slow, voltage-dependent process with striking similarity to slow inactivation, an intrinsic gating mechanism of Na+ channels. This process is strictly associated with neuronal activity and develops over seconds, endowing neurons with a novel form of cellular plasticity shaping synaptic integration, dendritic electrogenesis, and repetitive discharge.

Original languageEnglish (US)
Pages (from-to)793-806
Number of pages14
JournalNeuron
Volume39
Issue number5
DOIs
StatePublished - Aug 28 2003

ASJC Scopus subject areas

  • Neuroscience(all)

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