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Mechanism of action of snake venom α-neurotoxins on nicotinic acetylcholine receptors of rabbit sympathetic ganglion neurons

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Abstract

Currents evoked by iontophoretic applications of acetylcholine and postsynaptic currents evoked by single stimulation of the cervical sympathetic nerve were recorded in neurons of the isolated rabbit superior cervical ganglion with membrane voltage clamped and muscarinic acetylcholine receptors blocked by atropine (10−6 M). The α-neurotoxins from snake venom (α-bungarotoxin and α-cobratoxin) in a concentration of 10−6 M caused an increase in amplitude (potentiation) of the acetylcholine current, inhibition of that current, or initial potentiation followed by inhibition, in different neurons. Spectral analysis of the fluctuations of this current showed that α-neurotoxins affect neither the current through a single channel nor the duration of the open state of long-living channels (evidently extrasynaptic), but they approximately double the duration of the open state of long-living channels. This last effect in all probability causes potentiation of the acetylcholine current. The α-neurotoxins also depressed the amplitude of the postsynaptic current evoked by sympathetic nerve stimulation (on average by 44%) and lengthened its decline (on average by 24%). It is postulated that α-neurotoxins may both block and modify activity of the receptor-channel complex in the neurons tested, lengthening the duration of its open state. This latter mechanism of action of α-neurotoxins is exhibited only in long-living channels, evidence that the phamacological properties of the two populations of channels connected with nicotinic acetylcholine receptors are not identical.

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A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 15, No. 4, pp. 377–383, July–August, 1983.

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Selyanko, A.A. Mechanism of action of snake venom α-neurotoxins on nicotinic acetylcholine receptors of rabbit sympathetic ganglion neurons. Neurophysiology 15, 275–280 (1983). https://doi.org/10.1007/BF01059867

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