Modification of synaptic transmission and sodium channel inactivation by the insect-selective scorpion toxin LqhalphaIT.
The peptide LqhalphaIT is an alpha-scorpion toxin that shows significant selectivity for insect sodium channels over mammalian channels. We examined the symptoms of LqhalphaIT-induced paralysis and its neurophysiological correlates in the house fly (Musca domestica). Injection of LqhalphaIT into fly larvae produced hyperactivity characterized by continuous, irregular muscle twitching throughout the body. These symptoms were correlated with elevated excitability in motor units caused by two physiological effects of the toxin: 1) increased transmitter release and 2) repetitive action potentials in motor nerves. Increased transmitter release was evident as augmentation of neurally evoked synaptic current, and this was correlated with an increased duration of action potential-associated current (APAC) in loose patch recordings from nerve terminals. Repetitive APACs were observed to invade nerve endings. The toxin produced marked inhibition of sodium current inactivation in fly central neurons, which can account for increased duration of the APAC and elevated neurotransmitter release at the neuromuscular junction. Steady-state inactivation was shifted significantly to more positive potentials, whereas voltage-dependent activation of the channels was not affected. The shift in steady-state inactivation provides a mechanism for inducing repetitive activity in motoneurons. The effects of LqhalphaIT on sodium channel inactivation in motor nerve endings can account both for increased transmitter release and repetitive activity leading to hyperactivity in affected insects.
Lee
D
D
Departments of Entomology and Neuroscience, University of California at Riverside, Riverside, California 92521, USA.
Gurevitz
M
M
Adams
M E
ME
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006793:Houseflies / Q000502:physiology*; D066298:In Vitro Techniques; D007814:Larva; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D010243:Paralysis / Q000139:chemically induced; D018408:Patch-Clamp Techniques; D012604:Scorpion Venoms / Q000494:pharmacology*; D026941:Sodium Channel Blockers; D013268:Stimulation, Chemical; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
C065190:LqhalphaIT toxin; D009498:Neurotoxins; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin