SLOW INHIBITION OF NA-(1NON-8ENYL)-5-(1NON-8ENYL)PYRROLIDINE (PYR9), A SYNTHETIC DERIVATIVE OF AN ANT VENOM ALKALOID( CURRENT IN CRAYFISH AXONS BY 2)

2,5-Dialkylpyrrolidines present in the venom of ants from the genus Mo nomorium are natural insecticides causing a flaccid paralysis. The mec hanism of action of 2(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of 2,5-dialkylpyrrolidines, has been investigated in vitro on preparations of the ventral nerve cord of the crayfish Pr ocambarus clarkii. Our results clearly indicate that Pyr9 blocks spike conduction without affecting the resting potential, Voltage-clamp exp eriments carried out on axons demonstrate that this blockade is due to a dual expression of Na+ current inhibition: a tonic inhibition devel oping slowly (90% of inhibition within 20 min for a Pyr9 concentration of 50 mu mol l(-1)) and independently of stimulation, and a phasic in hibition developing during repetitive stimulation (5Hz), the accumulat ion kinetics of which is 0.072 pulse(-1) at 5Hz, according to the Cour tney model, These findings suggest that tonic and phasic inhibition ar e due to different mechanisms. In addition, Pyr9 induces a shift of th e Na+ inactivation curve towards more hyperpolarized potentials, which is in agreement with a higher affinity of Pyr9 for inactivated than f ar resting Na+ channels.