Ion fluxes through the sodium channels of garfish olfactory nerve membranes

1. The efflux of (22)Na from garfish olfactory nerves, after treatment with ouabain and equilibration with (22)Na, occurs in two components of almost equal size. One component represents efflux from the extracellular space and the other, much slower, component represents efflux from the intracellular space through the axonal membrane.2. The rate of efflux of (22)Na through the membrane is increased from 0.038 to 0.055 min(-1) by veratrine, and restored back to 0.036 min(-1) by the additional application of tetrodotoxin or saxitoxin (10(-7)M).3. 50% inhibition of this increased sodium ion flux occurs at tetrodotoxin and saxitoxin concentrations of 12 and 6 nM respectively.4. The tetrodotoxin-sensitive efflux of (22)Na is almost unchanged in nerves equilibrated with hypertonic 0.85 M-NaCl, whereas it is largely eliminated in nerves equilibrated with 0.85 M-LiCl. We interpret this to indicate that there exists within the sodium channel a specific metal cation site which is responsible for the co-ordination of the ions during their passage through the membrane. Lithium ions bind to this site relatively strongly, with a dissociation constant of 0.2-0.3 M, whereas sodium ions bind less strongly, with a dissociation constant greater than 0.75 M. Other evidence indicates that this site is the site at which tetrodotoxin and saxitoxin act.5. Batrachotoxin has a similar action to veratrine but is effective in concentrations at least 100 times lower.