EFFECTS OF ALPHA-POMPILIDOTOXIN ON SYNCHRONIZED FIRING IN NETWORKS OFRAT CORTICAL-NEURONS

We studied the effect of a novel neurotoxin, alpha-pompilidotoxin (alp ha-PMTX) on the spontaneously synchronized network firing of cultured rat cortical neurons. alpha-PMTX acted immediately and irreversibly to disrupt synchronous activity, leaving only residual sparse, uncorrela ted firing and was effective at concentrations of 10 nM. In the presen ce of bicuculline to block inhibitory synaptic transmission, the shutd own in synchronized activity occurred with a significant delay, requir ed a higher concentration of alpha-PMTX (>100 nM), and was preceded by a tr;transiently increased level of firing. It appears that both inhi bitory and excitatory neuronal activity or synaptic transmission are a mplified by alpha-PMTX, but that intense activity eventually leads to inactivation or transmitter depletion. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.