More than a quater century ago, investigation of an artificial membrane had a significant influence on the research of biological membrane theoretically and biologically. Nernst-Planck equation, Donnan equilibrium, Goldman-Hodgkin-Katz equation, phenomenological equation based on nonequilibrium thermodynamics had played an important role for the explanation of transport phenomena through biological membrane and the development of ion-exchange membranes. Recently, understanding of structure on membrane protein has been more and more facilitated.Therefore it will be possible to investigate the transport phenomena of ions through channel protein in the field of molecular theory and explain the mechanism of gating precisely. In this review the way how to approach the problems in channel protein and gate is discussed from the viewpoint of artificial membrane research.

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The hydrophobic environment of the lipid membrane bilayer is virtually impermeable to ions in aqueous solution. Protein channels permit the rapid flux of ions across membranes. Ion channels have a common structural motif, the transmembrane α-helix. In its most energetically favorable form the protein must be configured such that its most hydrophilic residues point toward the aqueous channel and its hydrophobic residues face the lipid bilayer. Voltage-gated ion channel for Na⁺ is constracted from a single large polypeptide chain. The polypeptide includes four internally homologous domains I-IV, each containing six hydrophobic membrane-spanning regions, S1-S6, that probably correspond to α-helices. These four interconnected domains are thought to arrange as a tetramer surrounding the voltage-gated ion channel. S4 is thought to fuction as the actual voltage sensor of depolarization that causes a conformational change to open the channel pore. A small pore size and the biochemistry of the pore lining conspire to determine the ion selectivity of a particular type of channel.

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A review is given on studies on the memebrane-ion interactions. There is an electrostatic energy barrier associated with the movement of an ion from a region of high dielectric constant (water, ε_??_80) through a region of low dielectric constant (lipid, ε_??_2). We discuss how the energy barrier can be lowered by “pores” and “carrieres”. It is shown that the pore energy is lower. In addition to the above long-range memebrane-ion interactions, there are short-range interactions between ions and dissociated gropus distributed within pores. Application to a Gramicidin A channel and a Na channel is also discussed.

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The voltage-gated sodium channels are responsible for the generation of conducted electrical signals in neurons and other excitable cells. The biphasic behavior of sodium permeability is described in terms of two experimentally separable gating processes that controls sodium channel functions, i.e., voltage-dependent activation and inactivation. The ion conductance of the activated sodium channels is both highly selective and remarkably efficient. Purification, molecular cloning and determination of the primary structure of the principal subunits of sodium channels has provided a molecular template for probing the relationships between structure and functions. Thus, this article reviewed the current status of research on the molecular basis of the three major elements of voltage-gated sodium channel functions, that is, voltage-dependent activation, sodium conductance and inactivation. Also, to enter the realm of the molecular physiology of the sodium channels, this article contains a brief, classical description of the channels.

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It is the best honor in my life as a researcher of membrane science to be accorded the 1995 young investigator's award by the Membrane Society of Japan. I would like to thank the president, Professor Takeo Shimizu and the persons concerning the award for their help.
The present review is based on the results of the investigation supervised by Professor Kiyotaka Sakai of Waseda University in his laboratory for about fouryears. I am also sincerely indebted to him and my collaborators.
A new method of determining solute permeability of a hollow-fiber dialysis membrane from absorbancy of a solution in the narrow lumen of the membrane using quartz optical fibers has been developed. Solute permeability of a single hollow-fiber membrane without the influence of convective solute flux was obtainable through the method.
Mass transfer coefficient around a single hollow-fiber membrane in ideal laminar flow was also determined by the method. Analogy between mass transfer and heat transfer in annular laminar flow was experimentally confirmed using the method.

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In the kidney, various anionic and cationic drugs are actively secreted from plasma to filtrate across proximal tubules. In addition, some drugs such as aminoglycoside antibiotics are accumulated selectively in the renal proximal tubular cells, which may be closely related with their nephrotoxicity. To understand the transport mechanisms of drugs in the kidney, we have used luminal (apical) brushborder and contraluminal basolateral membrane vesicles isolated from renal cortex. We have also established the in vitro model system to study the transcellular transport and the endocytic uptake of organic ions in intact cells using cultured renal cells. The present article concerns the transport of p-aminohippurate (an organic anion) in renal brush-border membrane vesicles and in OK cells, a cell line derived from the American opossum kidney, and that of gentamicin (an aminoglycoside antibiotic) in LLC-PK1 cells, a cell line derived from pig kidney. These studies with isolated membrane vesicles and cultured cells should provide useful information for the better understanding of mechanisms of organic ion transport in the kidney.

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The present paper reviews ion separation by charged reverse osmosis and nanofiltration membranes on the basis of the author's research work. The separation mechanism of charged reverse osmosis and nanofiltration membranes is based mainly considered to be on both electrostatic (charged) and sieve effects. First, ion separation ability by charge effect was investigated in the system where sieve effect is negligible. In single electrolyte solutions, electrolytes having divalent coions were rejected more than other types of electrolytes such as mono-monovalent electrolytes. In mixed electrolytes having common counterions, divalent coions were rejected much more than monovalent coions therefore, the separation of coions by charged membranes in reverse osmosis was found to be possible. On the other hand, the separation of counterions was not satisfactory based on the valence types. The experimental results were well explained by using the extended Nernst-Planck equation which considers the contribution of volume flow to the ion transport through charged membranes. Secondly, bipolar membranes were proposed in order to improve ion selectivity based on the valence types of ions. Positively charged layer was formed on a negatively charged layer. Experimental and theoretical investigation revealed that the separation of mono- and divalent ions was achieved by bipolar membranes in reverse osmosis. The bipolar membrane was also found experimentally and theoretically to be successfully applied to separate ions of sea water. Finally, a new model is proposed by considering both charge and sieve effects. Ion distribution, the diffusion and the coupling with volume flow are restricted due to steric-hindrance effect (sieve effect) in the system where the sieve effect cannot be negligible. The electrostatic and steric-hindrance model was formulated by modifying the extended Nernst-Planck equation, and supported by permeation experiments of organic electrolytes with a supporting electrolyte salts (sodium chloride.)

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In order to solve the problems in fouling and antithrombus, it is important to measure the permittivity and the conductivity of polymers adsorbed on hydrophobic and hydrophilic membranes. However, it has not been able to make acculate measurement of the capacitance of membranes adsorbing polymers at low frequency, because of the electrode polarization. We, thus, have utilized the 4 terminals method where the voltage and the electric current were mesured by using different elecrodes, to minimize the effect of electrode polarization. Using the above method, we measured the dielectric relaxation of Polycarbonate (PC) and Poly (tetrafluoroetylene) (PTFE) membranes adsorbing Poly (vinylpyrrolidone). In case of the PC membranes, the dielectric relaxation was not observed. On the other hand in case of the PTFE membranes, the relaxation was observed only when the amount of Polyvinylpyrrolidone was small. The permittivity of membrane was independent of the amount of adsorbed polymer, on the other hand, the conductivity of the membrane increased with increasing the adsorbed polymer, indicating that the hydrophobic membranes turned to hydrophylic.

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Asymmetric polyimide Kapton^®membranes were made by casting a solution of 18 wt% polyamic acid and 5 wt% phenanthrane in dimethylacetamide. The fluxes of ethylbenzene and hexane obtained with the mixtures with CO₂ were 1.2-1.4 times higher than those for pure solutes respectively. The measured separation factors, α (ethylbenzene/hexane), were 1.86 at 323K, 1.93 at 373K and 1.81 at 423K and found to be practically independent of the temperatures and the pressures.

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Transdermal Therapeutic System (TTS) which controls drug release by a membrane has been introduced. The system consists of five parts, that is, a backing film, a drug reservoir, a control membrane, an adhesive layer and a release liner. The release of nitroglycerin from the system is almost nearly zero order, enabling a constant drug administration to the body for over 24 hours. The control membrane material (ethylene-vinyl acetate copolymer) was also briefly described.

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