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Publication : Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance.

First Author  Swensen AM Year  2005
Journal  J Neurosci Volume  25
Issue  14 Pages  3509-20
PubMed ID  15814781 Mgi Jnum  J:98597
Mgi Id  MGI:3579194 Doi  10.1523/JNEUROSCI.3929-04.2005
Citation  Swensen AM, et al. (2005) Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. J Neurosci 25(14):3509-20
abstractText  Cerebellar Purkinje neurons often generate all-or-none burst firing in response to depolarizing stimuli. Voltage-clamp experiments using action potential waveforms show that burst firing depends on small net inward currents that flow after spikes and reflect the net balance between multiple large currents. Given this, burst firing is surprisingly robust in the face of changes in the magnitude of the underlying currents from cell to cell. We explored the basis of this robustness by examining the effects of reducing the sodium current, the major contributor to the postspike inward current. Burst firing persisted in concentrations of tetrodotoxin that produced half-block of sodium current. This robustness of bursting reflects an acute feedback mechanism whereby waveform changes from the reduced sodium current (reduced spike height and a hyperpolarizing shift in postspike voltage) cause compensatory decreases in postspike potassium currents. In particular, reduced spike height reduces calcium entry and subsequent calcium-activated potassium current, and the hyperpolarizing shift in postspike voltage speeds deactivation of Kv3-like potassium channels. Other experiments examined bursting in Na(v)1.6-/- mice, in which sodium current density is reduced in the long term. Under these circumstances, there was upregulation of both T-type and P-type calcium current and a change in the balance of calcium current and calcium-activated potassium current such that their net influence shifted from being inhibitory during bursts in wild-type neurons to excitatory during bursts from Na(v)1.6-/- mutant neurons. Thus, Purkinje neurons have both acute and long-term feedback mechanisms that serve to maintain burst firing when voltage-dependent sodium conductance is reduced.
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