Neuroscience 2004 Abstract
| Presentation Number: | 397.2 |
|---|---|
| Abstract Title: | Electrophysiological correlates of motor disorders produced by deletion of the Na channel <I>scn8a</I> exclusively in cerebellar Purkinje cells. |
| Authors: |
Aman, T. K.*1
; Grieco, T. M.1
; Khaliq, Z. M.1
; Levin, S. I.2
; Meisler, M. H.2
; Raman, I. M.1
1Inst for Neurosci, Northwestern Univ, Evanston, IL 2MI, 2205 Tech Dr. NBP, 60208, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Ion Channels -- Sodium Channels: Physiology |
| Session: |
397. Sodium Channels: Physiology I Poster |
| Presentation Time: | Monday, October 25, 2004 9:00 AM-10:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # I27 |
| Keywords: | RESURGENT, NAV1.6, SPONTANEOUS FIRING, ACTION POTENTIAL |
Scn8a encodes the NaV1.6 voltage-gated sodium channel α subunit. In cerebellar Purkinje neurons, expression of NaV1.6 produces channels that carry TTX-sensitive transient and resurgent current. Scn8a null mice, which lack NaV1.6, have severe motor deficits and die prematurely. The extent to which the pathophysiology results specifically from the change in Na currents in Purkinje neurons, however, is unknown. Recently, mice with Scn8a deleted exclusively in Purkinje neurons were generated. These animals are viable, but show impaired performance on specific motor tasks (S.I. Levin et al., SFN abstract 2004). Here, we have studied Na currents and spiking in Purkinje neurons of adult mutant mice lacking expression of NaV1.6 only in these cells. Transient and resurgent Na currents were elicited in Purkinje neurons acutely dissociated from 7-8 week old mutant animals and wild-type siblings. Relative to wild-type cells (N=5), transient current in mutant cells (N=16) was reduced by 44% (p<0.05). The resurgent current, however, was nearly twice as sensitive to the loss of Scn8a, decreasing by 82% (p<0.005). Current-clamp recordings from Purkinje neurons in cerebellar slices (35°C) revealed a reduced rate of spontaneous firing in mutant cells (9 ± 9 spikes/s, N=4) relative to wild-type cells (61 ± 16 spikes/s, N=5, p<0.05). The maximal firing rate was also decreased, from 236 ± 23 spikes/s (wild-type) to 97 ± 16 spikes/s (mutant, p<0.005). The correlation between the amplitude of resurgent current and the firing rate of Purkinje neurons provides further evidence for a role of this current in maintaining high-frequency activity in these cells. Further, the ataxic phenotype of these mutant mice suggests that Na channels with resurgent kinetics in Purkinje neurons are necessary for normal motor function.
Supported by NS39395, NS34509
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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