Depolarizing after-potentials

During the early phase of poisoning, the main effect of the insecticide is to induce a depolarizing after-potential of long duration, membrane depolarization (which was calculated for each concentration) being restricted to a few mV. As in the actual experiments, the size and duration of the afterpotential increased with insecticide concentration. 

Certain pyrethroids such as pyrethrins, allethrin and tetramethrin stimulate and then paralyze insects. Various nerves were stimulated to produce repetitive discharges either spontaneously or in response to a single stimulus (1-J>). The depolarizing after-potential was elevated by the pyrethroids and reached the threshold for repetitive after-discharges ( ,Z). At high concentrations of pyrethroids the membrane was gradually depolarized and impulse conduction was eventually blocked (f>,Z) Repetitive responses in the postsynaptic element in the pyrethroid-poisoned preparations were induced at the presynaptic nerve terminals (8.-1Q). Thus the nerve membrane appears to be the major target site of pyrethroids. 

Calculations show that only a very small fraction of sodium channels, less than 1%, needs to be modified by tetramethrin in order to elevate the depolarizing after-potential to the level of threshold for repetitive after-discharges (19). This represents a unique amplification of the toxicological effect from channel modulation to the symptoms of poisoning in animals, and accounts in part for the high potency of the pyrethroids. 

As shown in Fig. 19B, SA spikes identical to those initiated by direct current injection are also observed on the depolarizing after-potentials which follow full-blown action potentials initiated by antidromic or orthodromic activation. The SA spikes superimposed on depolarizing afterpotentials can give rise to bursts of full-blown action potentials. Occasionally, the full-blown action potentials (Fig. 20) evoked by perforant path... 

Fig. 20. SA spikes depolarizing after-potentials. Hyperpolarizing current injected through the recording electrode enhances the amplitude of the depolarizing after-potential until all-or-none SA spikes evoked by the after-potential initiate full-blown action potentials.

Assaf, S. Y., and Kelly, J. S., 1979, In the nature of depolarizing after-potentials in granuli cells of the rat dentate gyrus maintained in vitro, J. Physiol. (London) 296 68P. 

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. 

Ulbricht W, Flacke W (1965) After-potentials and large depolarizations of single nodes of Ranvier treated with veratridine. J Gen Physiol 48 1035-1046 Ulbricht W, Stoye-Herzog M (1984) Distinctly different rates of benzocaine action on sodium channels of Ranvier nodes kept open by chloramine-T and veratridine. Pflugers Arch 402 439-445... 

In our hands (Assaf et ai, 1981), depolarizing as opposed to hyper-polarizing after-potentials, 15-20 msec in duration, are a conspicuous feature of action potentials recorded in granule cells with resting mem-... 

Fig. 19. Small-amplitude spikes recorded intracellularly from granule cells. (A) Trains of SA spikes to be initiated by intracellular injections of depolarizing ramps of current through the recording electrode. Full-blown action potentials are initiated only at higher thresholds which are reached by increasing the slope of the ramps. (B) Antidromic action potentials and associated after-potentials evoked by stimulation in the CAS region near threshold for antidromic invasion (15 V, 50 sec). In the first trace failure of the action potential at the same stimulus intensity causes the after-potential to disappear and reveals the stimulus artifact. The after-potential gives rise to either SA spikes (arrow) or full-blown action potentials. In (C) a SA spike is evoked in the same cell by the intracellular injection of depolarizing current through the recording electrode. (From Assaf et al, 1981.)...

Figure 19-7 shows off potential measurements as an example, in which the 100-mV criterion, No. 3 in Table 3-3, as well as the potential criterion t/ ff < is fulfilled. It has to be remembered with off potential measurements that according to the data in Fig. 3-6, depolarization is slower with age, so that the 100 mV criterion must lead to errors with a measuring time of 4 hours. Off potential measurements should be carried out after commissioning at 1-, 2-, 6- and 12-month intervals and then annually. 

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