title: Endogenous bursting due to altered sodium channel function in rat hippocampal CA1 neurons.
abstract: Intracellular recordings were obtained from pyramidal neurons in the rat hippocampal CA1 area in order to investigate membrane mechanisms involved in veratridine-induced epileptiform activity. Veratridine (0.03-0.2 microM) caused no changes in the passive membrane parameters including the resting potential, input resistance, and time constant. In the presence of small doses (0.03-0.1 microM) of veratridine, a single stimulus caused a relatively slow, large, synaptic-independent potential called the slow depolarizing after-potential (SDAP). When the hippocampal slice was treated with higher doses of veratridine (over 0.1 microM), bursting, or seizure-like activity (SLA) occurred in response to a brief super threshold intracellular stimulation. The duration of SLA bursting could be as long as ten seconds depending on the amplitude of SDAP, and was independent of the stimulus strength or duration. The frequency and configuration of SLA were sensitive to changes in membrane potential caused by applied DC current. At 0.3 microM or higher, veratridine induced spontaneous rhythmic bursting that was also sensitive to membrane potential changes. The evoked or spontaneous bursting is characterized by being: (1) independent of synaptic transmission in that it persisted after complete blockade of evoked synaptic potential with kynurenic acid (0.5 mM), (2) sensitive to selective inhibition by low doses of the specific sodium channel blockers tetrodotoxin (TTX) or cocaine with no apparent influence on the evoked action potential. These results indicate that endogenous SLA bursting can be induced in hippocampal CA1 pyramidal neurons when certain properties of sodium channels are altered by veratridine.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, TX 77204-5515, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Tian
authors.forename: S
authors.initials: S
authors.lastname: Otoom
authors.forename: K A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*; D014701:Veratridine / Q000494:pharmacology
chemical_list: D015222:Sodium Channels; D014701:Veratridine