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Biomedical subjects

G N Ling

Publications and source records attributed to G N Ling.

At least 73 records · Page 4Linked to original sources

Oxidative phosphorylation and mitochondrial physiology: a critical review of chemiosmotic theory, and reinterpretation by the association-induction hypothesis.

Fundamental assumptions of the chemiosmotic hypothesis of Mitchell are examined. Comparison of these assumptions with experimental data accumulated over the past fifty years leads to the conclusion that the hypothesis has not been supported. A review of important findings concerning the physical state of the major intracellular cation potassium shows clearly that this ion does not exist in a free state but is adsorbed on specific anionic sites. These findings refute the membrane-pump theory but added powerful support for the association-induction hypothesis, on the basis of which a new mechanism of oxidative phosphorylation as well as a wide variety of mitochondrial behaviors are proposed and compared with experimental data.

Adenosine Triphosphate↗

Active solute transport across frog skin and epithelial cell systems according to the association-induction hypothesis.

The phenomenon of transport of ions, sugars, amino acids, etc. across frog skin and other epithelial systems has been commonly interpreted on the basis of the membrane-pump theory, according to which asymmetry in solute distribution as well as transport into and out of all living cells results from the permeability properties and "pump" activities of the membrane. In the present review, certain findings in the field of transepithelial transport of solutes are given new interpretation on the basis of molecular mechanisms introduced in the association-induction hypothesis, according to which "active transport" of solutes occurs only across bifacial cell systems like frog skin and intestinal epithelium but not in the maintenance of steady levels of solutes in unifacial cell systems such as muscle, nerve, and red blood cells.

Animals↗

Nuclear magnetic resonance relaxation and water contents in normal mouse and rat tissues and in cancer cells.

By studying nuclear magnetic resonance water proton spin-lattice relaxation times (T1 and T2) of normal mouse and rat tissues at varying water contents and by comparing the data with those obtained from five types of cancer cells in ascites form, we concluded that differences in total water contents between normal tissues and cancer cells contribute less than 10% to the differences between the longer T1 of cancer cells as compared to the T1 of normal tissues. In spite of the diverse origin of the five types of cancer cells studied, their T1 and T2 as well as water contents were confined within relatively narrow limits. We suggested that all 5 ascites tumors studied are maximally deviated and that the physical state of the water in all maximally deviated cancer cells is very similar.

Animals↗

Underestimation of Na permeability in muscle cells: implications for the theory of cell potential and for energy requirement of the Na pump.

A new method permits, in a complex efflux curve from living cells, identification of the fraction of labeled solute rate-limited by intracellular-extracellular exchange. Using this method, it was found that in Na+ efflux from frog voluntary muscle, the slow fraction conventionally described as rate-limited by membrane permeability is wrongly assigned. Instead, a much faster fraction, usually camouflaged by the efflux of labeled Na+ in the extracellular space, represents the exchange of intra- and extracellular Na+ rate-limited by cell surface permeation. Quantitatively, the result shows that the Na+ permeability constant has up to now been underestimated by a factor of 10. Implications of that finding for the theory of the resting potential, and the minimum energy required of resting frog muscles, are discussed.

Animals↗

Maintenance of low sodium and high potassium levels in resting muscle cells.

1. Previous work has shown that a frog sartorius muscle consists of parallel cells running all the way from one end of the muscle to the other and that amputation of one end of the muscle is not followed by regeneration of a new cell membrane. If now only the cut end of the amputated muscle is exposed to a Ringer solution in which the solutes 42K and 22Na act as radioactive labels and the rest of the cell is suspended in air, we have what is described as an effectively membraneless open-ended cell or EMOC preparation. In this case the only remaining anatomically intact plasma membrane and pumps are made nonfunctional by the removal of 'sources' for inward pumps and 'sinks' for outward pumps. 2. The healthy region of a frog sartorius muscle EMOC preparation continues to accumulate labelled K+ to a level higher than that in the Ringer solution and to exclude labelled Na+ to a level below that in the Ringer solution, much as a normal uncut muscle does in its normal environment. The differences were reduced by inclusion of ouabain in the medium. 3. The diffusion coefficient of Na+ in the normal muscle cytoplasm at 25 degrees C was measured using two methods. The average diffusion coefficient measured was 2.07 X 10(-6) cm2/sec, roughly 1/6 that of the diffusion coefficient of Na+ in a 0.1 N-NaCl solution. 4. The data obtained are discussed in terms of the association-induction hypothesis. In this theory asymmetrical solute distribution, basically an expression of a non-energy consuming metastable equilibrium state, is the result of specific combinations of two opposing mechanisms: adsorption which raises the level of the intracellular solute; and exclusion from cell water which tends to lower it.

Animals↗

How does reduced external K+ concentration affect the rate of Na+ efflux? Evidence against the K-Na coupled pump but in support of the association-induction hypothesis.

Recent frog-muscle studies produced the following findings: 1. Contrary to the theory of K+--Na+ coupled pump, reduction of external K+ concentration to near zero did not significantly reduce the rate of efflus of the fraction of cell Na+ conventionally regarded as rate-limited by membrane permeability. 2. Reduction of external K+ concentration profoundly reduced the rate of the efflux of this fraction only if the muscles were exposed to the low K+ while being loaded with radioactive Na+. 3. The data indicate that the fraction of Na+ efflux which in normal cells at room temperature has a half-time exchange (t1/2) of 20-40 min is not rate-limited by membrane permeability but by desorption from cellular adsorption sites. Surface-limited Na+ exchange between free Na+ in the cell and the external environment is represented by a faster fraction with a t1/2 of 2 to 4 min. 4. The data further indicate that the slow-down of the rate of efflux of the (slow) fraction arises from a cooperative shift of those beta- and gamma-carboxyl groups from adsorbing K+ to adsorbing Na+ when external K+ concentration is reduced below a critical level. The enhanced adsorption energy of the newly adsorbed Na+ raises the activation energy, hence a slower rate of exchange is seen as a slow-down in the "efflux curves." It is therefore only when free labeled Na+ is present in the cell water and thus available to the newly emerging Na+ adsorption sites that the effect of low external K+ can be visualized in a labeled-Na+ efflux study. Application of low K+ Ringer's solution after free labeled Na+ in and out of the cells has been washed away only causes enhanced adsorption of non-labeled Na+, which is not detected in isotope efflux study.

Animals↗

Experimental verification of an expected relation between time of incubation and magnitude of the fast and slow fractions of the sodium efflux from amphibian eggs.

The Na+ efflux curves of single ovarian eggs are separable into two fractions. The magnitude of the slow fraction increases slowly with time of exposure of the eggs to labeled Na+, long after the fast fraction has reached equilibrium. The data agree with the theory that the fast fraction is rate-limited by surface permeation and that the slow fraction is rate-limited by desorption from intracellular adsorption sites.

Animals↗

Thallium and cesium in muscle cells compete for the adsorption sites normally occupied by K+.

It was shown that Tl+ can stoichiometrically displace K+ in frog muscle cells. This displacement is independent of the function of cell membrane and postulated pumps and of a macroscopic electric charge or Donnan effect. It follows that Cs+ and Tl+ compete for the adsorption sites normally occupied by K+. On this basis, the association-induction hypothesis predicts that Cs+ and Tl+, like K+, should be primarily localized in the A-band of the muscle myofibrils.

Adsorption↗

The functions of polarized water and membrane lipids: a rebuttal.

In 1973, experimental evidence was reported in support of the view that water polarized in multilayers rather than simple lipid is responsible for the semipermeable properties of living cell membranes. The present article presents a full rebuttal to a subsequent attack on that view.

Biological Transport, Active↗