title: An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus.
abstract: Brain damage causes multiple changes in synaptic function and intrinsic properties of surviving neurons, leading to the development of chronic epilepsy. In the widely used pilocarpine-status epilepticus (SE) rat model of temporal lobe epilepsy (TLE), a major alteration is the marked increase in the fraction of intrinsically bursting CA1 pyramidal cells. Here we have differentiated between two types of bursting phenotypes: 1) bursting in response to threshold-straddling excitatory current pulses (low-threshold bursting) and 2) bursting only in response to suprathreshold stimuli (high-threshold bursting). Low-threshold bursting prevailed in 46.5% of SE-experienced neurons sampled 1-4 wk after pilocarpine-SE, but was rarely seen in control neurons (1.9%). As previously shown, it appeared to be driven predominantly by a T-type Ca(2+) current (I(CaT)) in the apical dendrites. After blocking low-threshold bursting with Ni(2+), the same neurons still manifested a high-threshold bursting phenotype. Another 40.1% of SE-experienced neurons displayed only a high-threshold bursting phenotype and the remaining 13.4% of these neurons were nonbursters. Altogether, high-threshold bursting prevailed in 86.6% of SE-experienced neurons, but only in 33.0% of control neurons. Several lines of evidence indicated that high-threshold bursting is driven by persistent Na(+) current (I(NaP)) at or near the soma. Congruently, I(NaP) was 1.5-fold larger in SE-experienced versus control neurons. We conclude that an increase in I(NaP), conjointly with an increase in I(CaT), strongly contributes to the predominance of bursting phenotypes in CA1 pyramidal cells early after pilocarpine-SE and thus likely plays a role in the development of a chronic epileptic condition in this TLE model.
authors.affiliation: Department of Medical Neurobiology, Hebrew University-Hadassah School of Medicine, P.O. Box 12272, Jerusalem 91121, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Chen
authors.forename: Hailing
authors.initials: H
authors.lastname: Su
authors.forename: Cuiyong
authors.initials: C
authors.lastname: Yue
authors.forename: Stefan
authors.initials: S
authors.lastname: Remy
authors.forename: Michel
authors.initials: M
authors.lastname: Royeck
authors.forename: Dmitry
authors.initials: D
authors.lastname: Sochivko
authors.forename: Thoralf
authors.initials: T
authors.lastname: Opitz
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Yoel
authors.initials: Y
authors.lastname: Yaari
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000009:adverse effects; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010862:Pilocarpine; D013779:Tetrodotoxin