A TTX-SENSITIVE CONDUCTANCE UNDERLYING BURST FIRING IN ISOLATED PYRAMIDAL NEURONS FROM RAT NEOCORTEX

Pyramidal neurons were acutely isolated from neocortex slices of 14- t o 20-day-old rats and patch-clamped under physiological conditions. Cu rrent-clamp recordings revealed firing patterns corresponding to those previously reported in slices as regular spiking (RS) and intrinsical ly bursting (IB), i.e., single action potentials (AP), trains of regul ar spikes and bursts with depolarizing after-potentials (DAP). In IB n eurons, intracellular perfusion with KF blocked the high-voltage-activ ated Ca2+ and the Ca2+-dependent K+ currents, revealing APs with a 10- 30 ms shoulder at -35 mV (shoulder AP), which was the supporting plate au of the intraburst spikes. The use of the A channel blocker, 4-amino pyridine, caused a three-fold reduction in the AP repolarizing rate. A study of the de- and repolarizing rates modulating the spike shape (s houlder AP, burst or single APs) suggested that the percentage of avai lable A channels could play a crucial role in burst formation. Blockad e of the residual T-type Ca2+ current by Ni2+ did not inhibit the AP s houlder, whereas it was completely and reversibly inhibited by 30 nM T TX, which did not affect AP amplitude. The AP rising rate was only hal ved by 100 nM TTX. The data concerning the A channel-mediated burst fo rmation and the role of the TTX-sensitive conductance have been succes sfully simulated in a model cell. We suggest that bursting is an intri nsic property of the membrane of neocortex neurons, and is sustained b y TTX-sensitive slowly inactivating and/or persistent Na+ conductances .