Use-dependent block with tetrodotoxin and saxitoxin at frog Ranvier nodes. II. Extrinsic influence of cations.
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 (La3+) 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 La3+ ions a larger, use dependence. The time constants of the current decline were 4-fold greater in 1.08 mM La3+. 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 on 1) the gating conformation of the channel, probably the inactivation and ii) the occupancy of a blocking site by di- or trivalent external cations.
Lönnendonker
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U
I. Physiologisches Institut der Universität des Saarlandes, Homburg/Saar, Federal Republic of Germany.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002412:Cations; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007811:Lanthanum / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008954:Models, Biological; D010539:Permeability; D011893:Rana esculenta; D011901:Ranvier's Nodes / Q000187:drug effects* / Q000378:metabolism; D012530:Saxitoxin / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
D002412:Cations; D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin; D007811:Lanthanum; D008274:Magnesium; D002118:Calcium