Interaction of monovalent cations with tetrodotoxin and saxitoxin binding at sodium channels of frog myelinated nerve.
Na currents and Na-current fluctuations were measured in myelinated frog nerve fibres to study interactions between monovalent externally applied cations and the binding of the Na-channel blockers tetrodotoxin (TTX) or saxitoxin (STX). Adding 110 mM NaCl to Ringer's solution increased the maximum peak Na conductance by a factor of 2.51 in the presence of 12 nM TTX and by a factor of 2.43 in the presence of 4 nM STX. According to the analysis of Na-current fluctuations this increase of the Na conductance is mainly caused by an increase of the number N of unblocked Na channels per node, while the conductance of a single channel saturates in the hyperosmolar solutions. The increase of N is interpreted by displacement of TTX or STX from Na channels by external Na+. Relief of TTX blockage was also observed by adding 110 mM chloride salts of Li+, hydrazine+, guanidine+ and K+ to Ringer, but not in Ringer + 110 mM tetramethylammonium chloride or 250 mM sucrose. The increase of N by the external cations is a saturating function of the permeability of the Na channel to these ions. The results are interpreted by a toxin receptor in a superficial prefilter to the Na channel, which contributes to cation discrimination at the outer channel region.
Lönnendonker
U
U
I. Physiologisches Institut der Universität des Saarlandes, Hamburg, Federal Republic of Germany.
Neumcke
B
B
Stämpfli
R
R
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002414:Cations, Monovalent / Q000378:metabolism*; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011893:Rana esculenta / Q000502:physiology*; D012530:Saxitoxin / Q000378:metabolism*; D012964:Sodium / Q000493:pharmacokinetics / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000378:metabolism*
D002414:Cations, Monovalent; D006834:Hydrazines; D015222:Sodium Channels; D013757:Tetraethylammonium Compounds; C029424:hydrazine; D012530:Saxitoxin; D013779:Tetrodotoxin; D008094:Lithium; D012964:Sodium; D011188:Potassium