title: Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents.
abstract: To fire at high rates, neurons express ionic currents that work together to minimize refractory periods by ensuring that sodium channels are available for activation shortly after each action potential. Vestibular nucleus neurons operate around high baseline firing rates and encode information with bidirectional modulation of firing rates up to several hundred Hz. To determine the mechanisms that enable these neurons to sustain firing at high rates, ionic currents were measured during firing by using the action potential clamp technique in vestibular nucleus neurons acutely dissociated from transgenic mice. Although neurons from the YFP-16 line fire at rates higher than those from the GIN line, both classes of neurons express Kv3 and BK currents as well as both transient and resurgent Na currents. In the fastest firing neurons, Kv3 currents dominated repolarization at all firing rates and minimized Na channel inactivation by rapidly transitioning Na channels from the open to the closed state. In slower firing neurons, BK currents dominated repolarization at the highest firing rates and sodium channel availability was protected by a resurgent blocking mechanism. Quantitative differences in Kv3 current density across neurons and qualitative differences in immunohistochemically detected expression of Kv3 subunits could account for the difference in firing range within and across cell classes. These results demonstrate how divergent firing properties of two neuronal populations arise through the interplay of at least three ionic currents.
authors.affiliation: Salk Institute for Biological Studies, Howard Hughes Medical Institute, Systems Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Aryn H
authors.initials: AH
authors.lastname: Gittis
authors.forename: Setareh H
authors.initials: SH
authors.lastname: Moghadam
authors.forename: Sascha
authors.initials: S
authors.lastname: du Lac
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D051670:Shaw Potassium Channels / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors; D014726:Vestibular Nuclei / Q000502:physiology*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D051670:Shaw Potassium Channels; D015222:Sodium Channels