A new class of neurotoxin from wasp venom slows inactivation of sodium current


: Professor N. Kawai, as above.
E-mail: kawainob@jichi.ac.jp


The effects of α-pompilidotoxin (α-PMTX), a new neurotoxin isolated from the venom of a solitary wasp, were studied on the neuromuscular synapses in lobster walking leg and the rat trigeminal ganglion (TG) neurons. Paired intracellular recordings from the presynaptic axon terminals and the innervating lobster leg muscles revealed that α-PMTX induced long bursts of action potentials in the presynaptic axon, which resulted in facilitated excitatory and inhibitory synaptic transmission. The action of α-PMTX was distinct from that of other known facilitatory presynaptic toxins, including sea anemone toxins and α-scorpion toxins, which modify the fast inactivation of Na+ current. We further characterized the action of α-PMTX on Na+ channels by whole-cell recordings from rat trigeminal neurons. We found that α-PMTX slowed the Na+ channels inactivation process without changing the peak current–voltage relationship or the activation time course of tetrodotoxin (TTX)-sensitive Na+ currents, and that α-PMTX had voltage-dependent effects on the rate of recovery from Na+ current inactivation and deactivating tail currents. The results suggest that α-PMTX slows or blocks conformational changes required for fast inactivation of the Na+ channels on the extracellular surface. The simple structure of α-PMTX, consisting of 13 amino acids, would be advantageous for understanding the functional architecture of Na+ channel protein.