A TTX-sensitive conductance underlying burst firing in isolated pyramidal neurons from rat neocortex.
Pyramidal neurons were acutely isolated from neocortex slices of 14- to 20-day-old rats and patch-clamped under physiological conditions. Current-clamp recordings revealed firing patterns corresponding to those previously reported in slices as regular spiking (RS) and intrinsically bursting (IB), i.e., single action potentials (AP), trains of regular spikes and bursts with depolarizing after-potentials (DAP). In IB neurons, intracellular perfusion with KF blocked the high-voltage-activated Ca2+ and the Ca(2+)-dependent K+ currents, revealing APs with a 10-30 ms shoulder at -35 mV (shoulder AP), which was the supporting plateau of the intraburst spikes. The use of the A channel blocker, 4-aminopyridine, caused a three-fold reduction in the AP repolarizing rate. A study of the de- and repolarizing rates modulating the spike shape (shoulder AP, burst or single APs) suggested that the percentage of available A channels could play a crucial role in burst formation. Blockade of the residual T-type Ca2+ current by Ni2+ did not inhibit the AP shoulder, whereas it was completely and reversibly inhibited by 30 nM TTX, which did not affect AP amplitude. The AP rising rate was only halved by 100 nM TTX. The data concerning the A channel-mediated burst formation and the role of the TTX-sensitive conductance have been successfully simulated in a model cell. We suggest that bursting is an intrinsic property of the membrane of neocortex neurons, and is sustained by TTX-sensitive slowly inactivating and/or persistent Na+ conductances.
Guatteo
E
E
Department of General Physiology and Biochemistry, University of Milan, Italy.
Franceschetti
S
S
Bacci
A
A
Avanzini
G
G
Wanke
E
E
D000818:Animals; D001369:Axons / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003198:Computer Simulation; D004594:Electrophysiology; D005459:Fluorides / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology*
D013779:Tetrodotoxin; D009532:Nickel; D005459:Fluorides