Use-dependent block with tetrodotoxin and saxitoxin at frog Ranvier nodes II. Extrinsic influence of cations |
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Authors: | U Lönnendonker |
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Institution: | (1) I. Physiologisches Institut der Universitat des Saarlandes, W-6650 Homburg/Saar, Germany;(2) Present address: Universitat Kaiserslautern, Fachbereich Biologie, Abteilung Allgemeine Zoologie, Postfach 3049, W-6750 Kaiserslautern, Germany |
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Abstract: | Use-dependent declines of Na+ currents in myelinated frog nerve fibres were measured during a train of depolarizing pulses in solutions containing tetrodotoxin (TTX) or saxitoxin (STX). The following effects of external monovalent (Na+), divalent (Ca2+, Mg2+) and trivalent (La2+) cations on use dependence were found: Increasing the Ca2+ concentration from 2 to 8 mM shifts its voltage dependence by 20 mV whereas no significant use-dependent decline occurred at 0.2 mM Ca2+. Doubling the external Na+ concentration in 0.2 mM Ca2+ solutions did not initiate phasic block. External Mg2+ ions induced a smaller, and La2+ ions a larger, use dependence. The time constants of the current decline were 4-fold greater in 1.08 mM La2+. The static block of Na+ currents by La3+ could be directly demonstrated by the relief of block during a train of pulses. The results are qualitatively explained by a toxin binding site at the Na+ channel whose affinity for TTX or STX depends oni) the gating conformation of the channel, probably the inactivation andii) the occupancy of a blocking site by di- or trivalent external cations. |
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Keywords: | Na+ channel Use dependence Tetrodotoxin Saxitoxin Myelinated nerve Cations |
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