title: Transmitter modulation of slow, activity-dependent alterations in sodium channel availability endows neurons with a novel form of cellular plasticity.
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 alpha 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.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Carr
authors.forename: Michelle
authors.initials: M
authors.lastname: Day
authors.forename: Angela R
authors.initials: AR
authors.lastname: Cantrell
authors.forename: Joshua
authors.initials: J
authors.lastname: Held
authors.forename: Todd
authors.initials: T
authors.lastname: Scheuer
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D011985:Receptors, Serotonin; D015222:Sodium Channels; D011494:Protein Kinases; D019204:GTP-Binding Proteins