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.