PUBLICATION

A non-inactivating high-voltage-activated two-pore Na⁺ channel that supports ultra-long action potentials and membrane bistability

Authors
Cang, C., Aranda, K., Ren, D.
ID
ZDB-PUB-170214-289
Date
2014
Source
Nature communications   5: 5015 (Journal)
Registered Authors
Keywords
Ion channels in the nervous system, Membrane potential, Synaptic transmission
MeSH Terms
  • Action Potentials*
  • Amino Acid Sequence
  • Animals
  • Cell Membrane/metabolism*
  • Molecular Sequence Data
  • Neurons/metabolism
  • Sequence Alignment
  • Voltage-Gated Sodium Channels/chemistry
  • Voltage-Gated Sodium Channels/genetics
  • Voltage-Gated Sodium Channels/metabolism
  • Xenopus Proteins/chemistry
  • Xenopus Proteins/genetics
  • Xenopus Proteins/metabolism
  • Xenopus laevis/genetics
  • Xenopus laevis/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
25256615 Full text @ Nat. Commun.
Abstract
Action potentials (APs) are fundamental cellular electrical signals. The genesis of short APs lasting milliseconds is well understood. Ultra-long APs (ulAPs) lasting seconds to minutes also occur in eukaryotic organisms, but their biological functions and mechanisms of generation are largely unknown. Here, we identify TPC3, a previously uncharacterized member of the two-pore channel protein family, as a new voltage-gated Na(+) channel (NaV) that generates ulAPs, and that establishes membrane potential bistability. Unlike the rapidly inactivating NaVs that generate short APs in neurons, TPC3 has a high activation threshold, activates slowly and does not inactivate-three properties that help generate long-lasting APs and guard the membrane against unintended perturbation. In amphibian oocytes, TPC3 forms a channel similar to channels induced by depolarization and sperm entry into eggs. TPC3 homologues are present in plants and animals, and they may be important for cellular processes and behaviours associated with prolonged membrane depolarization.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping