ENDOGENOUS BURSTING DUE TO ALTERED SODIUM-CHANNEL FUNCTION IN RAT HIPPOCAMPAL CA1 NEURONS

Intracellular recordings were obtained from pyramidal neurons in the r at hippocampal CA1 area in order to investigate membrane mechanisms in volved in veratridine-induced epileptiform activity. Veratridine (0.03 -0.2 mu M) caused no changes in the passive membrane parameters includ ing the resting potential, input resistance, and time constant. In the presence of small doses (0.03-0.1 mu M) of veratridine, a single stim ulus caused a relatively slow, large, synaptic-independent potential c alled the slow depolarizing after-potential (SDAP). When the hippocamp al slice was treated with higher doses of veratridine (over 0.1 mu M), bursting, or seizure-like activity (SLA) occurred in response to a br ief super threshold intracellular stimulation. The duration of SLA bur sting could be as long as ten seconds depending on the amplitude of SD AP, and was independent of the stimulus strength or duration. The freq uency and configuration of SLA were sensitive to changes in membrane p otential caused by applied DC current. At 0.3 mu M or higher, veratrid ine induced spontaneous rhythmic bursting that was also sensitive to m embrane potential changes. The evoked or spontaneous bursting is chara cterized by being: (1) independent of synaptic transmission in that it persisted after complete blockade of evoked synaptic potential with k ynurenic acid (0.5 mM), (2) sensitive to selective inhibition by low d oses of the specific sodium channel blockers tetrodotoxin (TTX) or coc aine with no apparent influence on the evoked action potential. These results indicate that endogenous SLA bursting can be induced in hippoc ampal CA1 pyramidal neurons when certain properties of sodium channels are altered by veratridine.