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Abstract

Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat.

J E Warnick, E X Albuquerque and C R Diniz
Journal of Pharmacology and Experimental Therapeutics July 1976, 198 (1) 155-167;
J E Warnick
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E X Albuquerque
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C R Diniz
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Abstract

When tityustoxin (TsTX, 1.43 muM; mol. wt. 6995) was applied to the rat phrenic nerve-diaphragm muscle preparation, both the directly and indirectly elicited muscle contractions were transiently potentiated by about 30 and 60%, respectively, and the half-relaxation time was prolonged to more than 10 times the control. The onset of potentiation of muscle contraction was immediate and coincided closely with the prolongation of the directly elicited action potential and depolarization of the muscle membrane but preceded the presynaptic effect of the toxin. TsTX antagonized the neuromuscular blockade produced by low concentrations of d-tubocurarine (6.5 muM) but not by higher concentrations of d-tubocurarine (13 muM) or by alpha-bungarotoxin (5 mug/ml). Single shocks to the nerve of toxin-treated muscles evoked repetitive end-plate potentials which summated and triggered action potentials and muscle contractions 15 minutes after exposure. After 25 minutes, the frequency of spontaneous transmitter release transiently increased from 2 to 550 sec-1 but was never blocked and there was no blockade of the acetylcholine receptors of chronically denervated muscle. Both the increase in miniature end-plate potential frequency and postsynaptic depolarization induced by TsTX could be blocked by tetrodotoxin, and the effects on end-plate potentials and action potentials could be blocked by lowering the external sodium concentration. Removal of calcium and addition of ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA, 10 mM) to the bathing fluid blocked the presynaptic but not postsynaptic effects of TsTX at 23 degrees C; at 37 degrees C the presynaptic effects of TsTX in a calcium-free medium with EGTA were depressed but still present. Delayed rectification and membrane electrical characteristics were unaffected by TsTX. The results indicate that TsTX depolarizes the pre- and postsynaptic membranes by increasing sodium permeability. The postsynaptic site of action is most likely to be the sarcolemmal membrane where TsTX delays Na inactivation and thus prolongs the active phase of muscle contraction. Presynaptically, TsTX has two sites of action: 1) it depolarizes the nerve terminal thus facilitating the spontaneous release of transmitter; and 2) it acts at the membrane of the unmyelinated nerve terminal arborizations where it prolongs the sodium current thus giving rise to a repetitive response to single shocks applied to the nerve.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 198, Issue 1
1 Jul 1976
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Abstract

Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat.

J E Warnick, E X Albuquerque and C R Diniz
Journal of Pharmacology and Experimental Therapeutics July 1, 1976, 198 (1) 155-167;

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Abstract

Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat.

J E Warnick, E X Albuquerque and C R Diniz
Journal of Pharmacology and Experimental Therapeutics July 1, 1976, 198 (1) 155-167;
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