Cells, nerve, repetitive discharges

In squid giant axons, PbTx causes a depolarization of the plasma membrane, repetitive discharges followed by depression of action potentials, and a complete blockade of excitability. This action is antagonized by TTX (83,84). PbTx depolarizes nerve terminals and induces neurotransmitter release (85,86) it depolarizes skeletal muscle cells (87) and increases the frequency of action potentials in crayfish nerve cord (88). PbTx also produces a contraction of the guinea pig ileum (89). All these effects are prevented by TTX. 

Veratrum alkaloids cause repetitive discharges of nerve cells, apparently by delaying repolarization (possibly by action on lipid components and an ATPase in the cell membrane) (Levinson, 1976). Veratridine (94) binds to the sodium channel and keeps it permanently open and active (Greenhill and Grayshan, 1992). Protoveratrines A and B inhibit inactivation of Na channels. Cevadine (95) and protoveratrines A and B (85,86) depolarize membranes (Wink, 1993). 

Intoxication with DDT results in ataxia, loss of coordination, convulsions, and hyperexcitation of insects and mammals. Various regions of the nervous system were stimulated to discharge repetitively either in response to a single stimulus or spontaneously. These included sensory cells, synapses, and nerve fibers (2.3.36.37). Repetitive after-discharges in nerve fibers were due to an increase in the depolarizing (negative) after-potential by DDT (M, 39). Repetitive responses in neuromuscular junctions have been shown to originate in presynaptic nerve terminals (40). It appears that DDT and pyrethroids exert similar effects on the nerve membrane sodium channel (41). Detailed analyses as described below clearly show that this is actually the case. 

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