THRESHOLD EXTRACELLULAR CONCENTRATION DISTRIBUTION OF PENICILLIN FOR GENERATION OF EPILEPTIC FOCUS MEASURED BY DIFFUSION ANALYSIS

The tissue volume required to produce a penicillin-induced interictal discharge in the local EEG was estimated. A pair of microelectrodes were lowered into the motor cortex of anaesthetised and artifically ventilated rats. One doubled-barrelled electrode was used to release tetramethylammonium (TMA +) by iontophoresis or to pressure eject a solution containing penicillin (PEN-) and TMA+ concentration. The extracellular distribution of PEN- was defined using diffusion analysis of the TMA+. From these data the spatial distribution of PEN- was estimated at the times of first interictal spikes in the EEG. The critical mass of active nerve cells was calculated from the threshold concentration of PEN- needed to elicit paroxysmal depolarisation shifts in neocortical slices and found to lie within a tissue sphere with a radius of ca. 150-mu-m.