2,5-Dialkylpyrrolidines present in the venom of ants from the genus Monomorium are natural insecticides causing a flaccid paralysis. The mechanism 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 Procambarus clarkii. Our results clearly indicate that Pyr9 blocks spike conduction without affecting the resting potential. Voltage-clamp experiments carried out on axons demonstrate that this blockade is due to a dual expression of Na+ current inhibition: a tonic inhibition developing slowly (90 % of inhibition within 20 min for a Pyr9 concentration of 50 µmol l-1) and independently of stimulation, and a phasic inhibition developing during repetitive stimulation (5 Hz), the accumulation kinetics of which is 0.072 pulse-1 at 5 Hz, according to the Courtney model. These findings suggest that tonic and phasic inhibition are due to different mechanisms. In addition, Pyr9 induces a shift of the Na+ inactivation curve towards more hyperpolarized potentials, which is in agreement with a higher affinity of Pyr9 for inactivated than for resting Na+ channels.
Slow inhibition of Na+ current in crayfish axons by 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of an ant venom alkaloid
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B Lebrun, D Cattaert; Slow inhibition of Na+ current in crayfish axons by 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of an ant venom alkaloid. J Exp Biol 1 January 1997; 200 (15): 2097–2106. doi: https://doi.org/10.1242/jeb.200.15.2097
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