Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro.
Most types of electrographic epileptiform activity can be characterized by isolated or repetitive bursts in brain electrical activity. This observation is our motivation to determine mechanisms that underlie bursting behavior of neuronal networks. Here we show that the persistent sodium (Na(P)) current in mouse neocortical slices is associated with cellular bursting and our data suggest that these cells are capable of driving networks into a bursting state. This conclusion is supported by the following observations. 1) Both low concentrations of tetrodotoxin (TTX) and riluzole reduce and eventually stop network bursting while they simultaneously abolish intrinsic bursting properties and sensitivity levels to electrical stimulation in individual intrinsically bursting cells. 2) The sensitivity levels of regular spiking neurons are not significantly affected by riluzole or TTX at the termination of network bursting. 3) Propagation of cellular bursting in a neuronal network depended on excitatory connectivity and disappeared on bath application of CNQX (20 microM) + CPP (10 microM). 4) Voltage-clamp measurements show that riluzole (20 microM) and very low concentrations of TTX (50 nM) attenuate Na(P) currents in the neural membrane within a 1-min interval after bath application of the drug. 5) Recordings of synaptic activity demonstrate that riluzole at this concentration does not affect synaptic properties. 6) Simulations with a neocortical network model including different types of pyramidal cells, inhibitory interneurons, neurons with and without Na(P) currents, and recurrent excitation confirm the essence of our experimental observations that Na(P) conductance can be a critical factor sustaining slow population bursting.
van Drongelen
Wim
W
Department of Pediatrics, The University of Chicago, Chicago, IL 60637-1470, USA. wvandron@peds.bsd.uchicago.edu
Koch
Henner
H
Elsen
Frank P
FP
Lee
Hyong C
HC
Mrejeru
Ana
A
Doren
Erin
E
Marcuccilli
Charles J
CJ
Hereld
Mark
M
Stevens
Rick L
RL
Ramirez
Jan-Marino
JM
D000818:Animals; D000831:Animals, Newborn; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000502:physiology; D008297:Male; D051379:Mice; D008959:Models, Neurological; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D019782:Riluzole / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D015222:Sodium Channels; D013779:Tetrodotoxin; D019782:Riluzole