Influence of Na+ and Li+ ions on the kinetics of sodium channel block by tetrodotoxin and saxitoxin.
Voltage clamp experiments were done on single myelinated frog nerve fibres. The rate of block of Na+ channels by tetrodotoxin (TTX) was obtained from changes in peak Na+ current during 1-Hz trains of depolarizing impulses. In hypertonic Na(+)-rich solution (216 mM) the stationary block was reduced compared with Na(+)-poor solutions (54 mM or less; tetramethylammonium ions substituting for Na+). Washout in 216 mM Na+ was faster than in 54 mM Na+. Concentration of Na+ [( Na+]) little affected onset of block. After equilibration in Na(+)-poor TTX solution, a sudden application of Na(+)-rich toxin solution led to a partial relief from block that proceeded faster than the onset in the latter solution. Comparable results were obtained with saxitoxin (STX) and in analogous Li+ solutions. Most of the observed phenomena could be quantitatively fitted by a cyclic model in which cations favour the transition of channels (unblocked and blocked) from a high- to a low-affinity state from which toxin dissociates faster.
Hansen
G
G
Physiologisches Institut, Universität Kiel, Federal Republic of Germany.
Ulbricht
W
W
D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008954:Models, Biological; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D011893:Rana esculenta; D012530:Saxitoxin / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin; D008094:Lithium; D012964:Sodium