title: Proximal persistent Na+ channels drive spike afterdepolarizations and associated bursting in adult CA1 pyramidal cells.
abstract: In many principal brain neurons, the fast, all-or-none Na+ spike initiated at the proximal axon is followed by a slow, graded after depolarization (ADP). The spike ADP is critically important in determining the firing mode of many neurons; large ADPs cause neurons to fire bursts of spikes rather than solitary spikes. Nonetheless, not much is known about how and where spike ADPs are initiated. We addressed these questions in adult CA1 pyramidal cells, which manifest conspicuous somatic spike ADPs and an associated propensity for bursting, using sharp and patch microelectrode recordings in acutely isolated hippocampal slices and single neurons. Voltage-clamp commands mimicking spike waveforms evoked transient Na+ spike currents that declined quickly after the spike but were followed by substantial sustained Na+ spike after currents. Drugs that blocked the persistent Na+ current (INaP), markedly suppressed the sustained Na+ spike after currents, as well as spike ADPs and associated bursting. Ca2+ spike after currents were much smaller, and reducing them had no noticeable effect on the spike ADPs. Truncating the apical dendrites affected neither spike ADPs nor the firing modes of these neurons. Application of INaP blockers to truncated neurons, or their focal application to the somatic region of intact neurons, suppressed spike ADPs and associated bursting, whereas their focal application to distal dendrites did not. We conclude that the somatic spike ADPs are generated predominantly by persistent Na+ channels located at or near the soma. Through this action, proximal INaP critically determines the firing mode and spike output of adult CA1 pyramidal cells.
authors.affiliation: Department of Physiology, Institute of Medical Sciences, Hebrew University-Hadassah Faculty of Medicine, Jerusalem 91120, Israel.
authors.forename: Cuiyong
authors.initials: C
authors.lastname: Yue
authors.forename: Stefan
authors.initials: S
authors.lastname: Remy
authors.forename: Hailing
authors.initials: H
authors.lastname: Su
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Yoel
authors.initials: Y
authors.lastname: Yaari
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels