Effects of alpha-pompilidotoxin on synchronized firing in networks of rat cortical neurons.

We studied the effect of a novel neurotoxin, alpha-pompilidotoxin (alpha-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, uncorrelated firing and was effective at concentrations of 10 nM. In the presence of bicuculline to block inhibitory synaptic transmission, the shutdown in synchronized activity occurred with a significant delay, required a higher concentration of alpha-PMTX (> 100 nM), and was preceded by a transiently increased level of firing. It appears that both inhibitory and excitatory neuronal activity or synaptic transmission are amplified by alpha-PMTX, but that intense activity eventually leads to inactivation or transmitter depletion.