A positive temperature coefficient is the term which has been used to indicate that an increase in solubility occurs as the temperature is raised, whereas a negative coefficient indicates a decrease in solubility with rise in temperature.

Effect of Temperature

Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physicochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an “aqueous-polar (pore) pathway” across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to >750, and log Koct ranging from −3 to + 6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values. Overall, then, we present a facile interpretation of a considerable body of skin permeability measurements that (a) very adequately describes the dependence of Kp upon permeant size and lipophilicity, (b) generates parameters of considerable physicochemical and mechanistic relevance, and (c) implies that the SC lipids alone can fully characterize the barrier properties of mammalian skin.

Predicting skin permeability.

The following topics are discussed: a summary of dielectric theory; amino acids, peptides, proteins and DNA; bound water in biological systems; biological electrolytes; membranes and cells; tissues.

/pdf/the-passive-electrical-properties-of-biological-systems-2tkz7wn98j.pdf

The passive electrical properties of biological systems: their significance in physiology, biophysics and biotechnology

Important constraints on possible molecular mechanisms of general anaesthesia are derived from a quantitative reappraisal of data on the potency of general anaesthetics on whole animals. Despite their popularity, theories that invoke lipids as the prime target do not look at all promising, and available data point much more plausibly to a direct effect on particularly sensitive proteins. Structural changes of proteins on binding general anaesthetics are probably small but may be sufficient to perturb normal function; alternatively, anaesthetics may compete with an endogenous ligand. The phenomenon of pressure reversal of anaesthesia may simply be due to anaesthetics being squeezed away from their target sites.

Molecular mechanisms of general anaesthesia

Neuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system. Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and enhanced neurotransmitter release, eventually followed by block of excitation, result from a prolongation of the sodium current during membrane excitation. This effect is caused by a stereoselective and structure-related interaction with voltage-dependent sodium channels, the primary target site of the pyrethroids. Near-lethal doses of pyrethroids cause sparse axonal damage that is reversed in surviving animals. After prolonged exposure to lower doses of pyrethroids axonal damage is not observed. Occupational exposure to pyrethroids frequently leads to paresthesia and respiratory irritation, which are probably due to repetitive firing of sensory nerve endings. Massive exposure may lead to severe human poisoning symptoms, which are generally treated well by symptomatic and supportive measures.

/pdf/neurotoxicological-effects-and-the-mode-of-action-of-mfikldv6ht.pdf

Neurotoxicological Effects and the Mode of Action of Pyrethroid Insecticides

Anaesthesia by the n-alkanes. A comparative study of nerve impulse blockage and the properties of black lipid bilayer membranes.

1. The electrical properties of squid giant axons were examined by means of admittance bridges at frequencies from 0.5 to 300 kHz. A simple equivalent circuit was used to estimate the membrane capacity. 2. The calculated membrane capacities decreased monotonically over the whole frequency range. 3. At 100 kHz and higher frequencies the membrane capacity was independent of potential. 4. At frequencies greater than 20 kHz, exposure of the axons to saturated or 0.9 saturated solutions of n-pentane (275-306 micrometer) reduced the capacity per unit area by 0.1-0.15 micro F cm-2. 5. At 1 kHz the effect of the saturated pentane solutions depended on the membrane potential. In axons having potentials between -60 and zero mV the pentane solutions lowered the capacity, whereas for potentials between -160 and -60 mV they produced little or no change. 6. Saturated solutions of n-hexane, n-heptane and n-octane exhibited qualitatively similar, but quantitatively smaller influences on the membrane capacity, the changes declining as the chain length increased. 7. Under voltage clamp, the peak inward and steady-state outward currents were partially suppressed by the hydrocarbons. Saturated solutions of n-pentane usually reduced the former (reversibly) by 60-80% and the latter by 20-40%. Solutions of n-hexane, n-heptane and n-octane appeared to have successively less effect. Except in deteriorating axons, none of the hydrocarbons produced any consistent changes in the passive membrane resistance, the resting potential or in the reversal potential of the transient inward current. 8. Both the changes in the clamp currents and in the membrane capacity were largely, though not usually completely, reversible. In the hydrocarbon solution the axons deteriorated more rapidly than normal. 9. The responses of axons of Doryteuthis plei to the hydrocarbons were very similar to those of Loligo forbesi with the exception that for the former all observed changes were some five times faster. 10. The time courses of the peak inward and steady-state outward currents on exposure of the axons to n-pentane resembled the time course of the change in membrane capacity at 100 kHz. 11. The simplest interpretation of the high frequency capacity results is suggested to be that, as for lipid bilayers, the membranes become thicker through adsorption of the hydrocarbon.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1980.sp013506

Some effects of aliphatic hydrocarbons on the electrical capacity and ionic currents of the squid giant axon membrane.

Using a microelectrophoretic method the zeta potentials of Bacterium coli suspended in a series of inorganic electrolytes having either a common anion or cation have been determined. By experiment, or extrapolation to zero potential of the curve of zeta potential against log 10 [electrolyte concentration], it has been possible to find the concentration (normality) of each electrolyte required to neutralize exactly the charge on the cells. For cations with common anions and vice versa, the ‘reversal of charge concentrations’ have been plotted in the form of spectra. Comparison with similar spectra given in Kruyt (1949 a ) for some naturally occurring substances has indicated that the exterior of the cells is polysaccharide, possibly an arabate. This conclusion is supported by the pK and isoelectric point derived from the curve of zeta potential against surface pH, and also by the relatively low zeta potentials exhibited by Bact. coli in detergents compared with the corresponding values for lipoidal substances.

Surface behaviour of Bacterium coli. I. The nature of the surface.

1. The effects of some neutral clinical and experimental general anaesthetics on the resting potential of normal squid axons and squid axons exposed to tetrodotoxin and 3,4-diaminopyridine have been studied. 2. Depolarizations of 1-4 mV were produced by all the anaesthetics at 'clinical' concentrations in the normal axon. Larger depolarizations (5-11 mV) were produced by the same anaesthetic concentrations in axons exposed to tetrodotoxin and 3,4-diaminopyridine. 3. The conductance of axons exposed to tetrodotoxin and either tetraethyl-ammonium or 3,4-diaminopyridine in zero Na+, 430 mM-K+ artificial sea water was examined by voltage clamp and AC bridge techniques. 4. The evidence that this conductance is due predominantly to K+ is discussed. 5. Pre-pulse protocols under voltage clamp have been used to show that part of this conductance arises from the incompletely blocked delayed rectifier. 6. Substantial reductions in this conductance are produced by anaesthetics at 'clinical' concentrations. 7. It is concluded that there is a component of the K+ conductance of the resting squid axon other than the Hodgkin-Huxley delayed rectifier which is extremely sensitive to anaesthetics and which to an appreciable extent determines the resting potential.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1988.sp017209

The potassium conductance of the resting squid axon and its blockage by clinical concentrations of general anaesthetics.

The effects of fourteen halogenated ethers on the sodium and potassium currents of voltage-clamped squid giant axons have been examined. Effects under open-circuit were also studied. In voltage-clamped axons, the ethers tended to reduce potassium currents at least as much, if not more, than sodium currents. This finding distinguishes the halogenated ethers from many other general anaesthetics. Certain, but not all, halogenated ethers induced a pronounced maximum in potassium current traces as a function of time. This property can be formally described if an inactivation term is added to the Hodgkin-Huxley equation for potassium currents. Large shifts in the sodium-current inactivation parameter h infinity were produced in some instances. Two fully halogenated methyl ethyl ethers, known to produce convulsions in mice, depressed both sodium and potassium currents, but with a very slow time course of action. The electrophysiological effects of the halogenated ethers investigated appear to depend on the position and number of hydrogen bonds that can be formed.

D A Haydon

Papers

Anaesthesia by the n-alkanes. A comparative study of nerve impulse blockage and the properties of black lipid bilayer membranes.

Some effects of aliphatic hydrocarbons on the electrical capacity and ionic currents of the squid giant axon membrane.

Surface behaviour of Bacterium coli. I. The nature of the surface.

The potassium conductance of the resting squid axon and its blockage by clinical concentrations of general anaesthetics.

The actions of halogenated ethers on the ionic currents of the squid giant axon