title: A non-inactivating high-voltage-activated two-pore Na⁺ channel that supports ultra-long action potentials and membrane bistability.
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.
authors.affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Cang
authors.affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Aranda
authors.affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Dejian
authors.initials: D
authors.lastname: Ren
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D016415:Sequence Alignment; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C000602320:TPC3 protein, Xenopus; D061566:Voltage-Gated Sodium Channels; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C000602319:tpcn3 protein, zebrafish