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Biomedical subjects

R Henderson

Publications and source records attributed to R Henderson.

At least 235 records · Page 13Linked to original sources
PubMed1974

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.

Animals↗
PubMed1973

The binding of labelled saxitoxin to the sodium channels in nerve membranes.

1. Tritium labelled saxitoxin has been prepared and purified, and its binding both to intact rabbit vagus nerves and to a solubilized preparation of garfish olfactory nerve membranes has been examined.2. In intact and solubilized nerves there is a saturable binding component of magnitude equal to that previously obtained for labelled tetrodotoxin.3. This component of bound saxitoxin is displaced competitively by tetrodotoxin, and it is concluded that the two toxins bind to the same site.4. The saturable saxitoxin (STX) interaction with the nerve membrane is reversible and can be described by the equation STX + R right harpoon over left harpoon STX.R where R is the binding site or receptor. With the solubilized preparation of garfish nerve membranes the saxitoxin-receptor reaction rates are almost four times faster than those of tetrodotoxin. The half-life of the saxitoxin-receptor complexes is 13 sec compared with 44 sec for the tetrodotoxin-receptor complex.5. A number of agents were tested for their ability to displace the labelled saxitoxin. Calcium and thallous ions each produced significant reversible reduction in binding, with apparent equilibrium dissociation constants of about 20-30 mM. Toxin binding is also inhibited reversibly in acidic solutions by protons competing with toxin for a binding site with a pK(a) of 5.6-5.9. All three ions are known to block sodium currents in myelinated nerve at similar concentrations. Our experiments indicate that they do so at the site of toxin binding.6. Lidocaine and veratrine do not affect the binding of saxitoxin.

Animals↗
PubMed1972

The binding of labelled tetrodotoxin to non-myelinated nerve fibres.

1. Tritiated tetrodotoxin has been prepared and purified, and its binding to rabbit, lobster, and garfish non-myelinated nerve fibres examined.2. In each case a component of the binding curve was found that saturated at concentrations of a few nanomolar.3. In addition, non-specific binding, indicated by a linear dependence of the amount bound on concentration, occurred.4. The kinetics of wash-in and wash-out of the radioactive toxin were consistent with a model in which all binding was rapid and reversible and in which diffusion into and out of the nerve bundle was rate-limiting. This was shown by numerical solution of the appropriate non-linear diffusion equation. An extension of the limited biophase model that allows for non-specific binding was shown to give good semiquantitative approximations to the proper diffusion equation; and (unlike the latter) the extension was shown to have a relatively simple solution.5. A number of pharmacological agents were tested for competition with, or perturbation of, tetrodotoxin binding: sodium, calcium and hydrogen ions, lidocaine, batrachotoxin and saxitoxin. Apart from a small calcium effect, only saxitoxin, whose effect on sodium current is similar to that of tetrodotoxin, was found to interfere with binding. Increasing saxitoxin concentrations resulted in reduced amounts of tetrodotoxin binding in a manner consistent with a competition between the two toxins for the same site.

Animals↗
PubMed1971

Catalytic activity of -chymotrypsin in which histidine-57 has been methylated.

The properties of a derivative of alpha-chymotrypsin in which histidine-57 has been methylated have been examined. Although the modified enzyme binds substrate with the same affinity as does native alpha-chymotrypsin, acylation and deacylation occur at much decreased rates. As for native alpha-chymotrypsin, a basic group of pK(a) approx. 7 is involved in both acylation and deacylation. The significance of these results is considered in relation to the normal function of histidine-57.

Acridines↗