Hypouricemia in Hodgkin's disease.
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Biomedical subjects
Publications and source records attributed to I Singer.
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The effect of tetrodotoxin on excitability of internally perfused squid giant axons immersed in various sodium-free media was examined. Action potentials were found to be suppressed by this substance, with or without sodium ion in the external medium. Tetrodotoxin showed a strong suppressive effect upon action potentials produced in media containing salts of only divalent cations (CaCl(2), CaBr(2), SrCl(2), or BaCl(2)). Our findings concerning the action of tetrodotoxin do not support the separate-channel hypothesis for excitable membranes.
Radiotracer techniques were used to study the influxes and effluxes of various univalent cations in internally perfused squid giant axons. Membrane currents and conductances were determined by the voltage-clamp technique under analogous internal and external conditions. Both sodium-containing and sodium-free internal and external media were studied. Membrane impedance was measured with an ac impedance bridge to determine the general magnitude and time course of the impedance loss which accompanied the excitation process in both varieties of external media. Maximum transmembrane currents were found to be of comparable magnitude to the charge transfer associated with the peak interdiffusion flux measured under the same conditions. The product of the membrane resistance and the interdiffusion flux remained constant over a wide range of resistance and flux values, both at rest and during activity, both in sodium-containing and sodium-free media. The implications of these findings for excitation theory are discussed.
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The effects of ten cations and fifteen anions on the excitability of the squid giant axon were studied. The method of intracellular perfusion used in these investigations is described in detail. Empirical criteria were established for evaluating the relative favorability of any salt solution for maintaining the normal excitability of the membrane of the axon. It was found that both cations and anions could be ordered in sequences of relative favorability, which are directly related to the classic lyotropic sequences found for protein macromolecules and in colloid chemistry in general. The effects of concentration, salt mixtures, non-electrolyte carriers, enzymes, metabolic inhibitors, pH, and external media were also studied. The results are interpreted in terms of current concepts of the interactions between water structure, charged macromolecules, and their ionic environments. A macromolecular approach is given to the physicochemical nature of the "two stable states" of the excitable membrane, to describe the time-dependent potential changes observed.