Contents:

I: The alkali metal ions in isolated systems and tissues.- I. General introduction.- II. Physical and chemical properties of the alkali metal ions.- a) Introduction.- b) Chemical properties.- c) Chemical binding.- d) Chelates with low-molecular anions.- e) Binding by ion exchange resins.- f) Binding by phosphate esters and polyphosphates.- g) Binding by nucleic acids.- h) Binding by polyvalent acid polysaccharides.- i) Binding by proteins.- III. Role of alkali metal ions in enzymatic processes.- a) Introduction.- b) Specific effects on enzymatic processes.- 1. Pyruvic phosphoferase.- 2. Fructokinase.- 3. Bacterial hexokinase.- 4. Phosphofructokinase.- 5. Acetate-activating enzyme (and "choline acetylase").- 6. Phosphotransacetylase.- 7. Glutathione synthesizing enzyme system.- 8. Aldehyde dehydrogenase (from yeast).- 9. ?-galactosidase (from Escherichia coli).- 10. Apyrase (brain adenosinetriphosphatase).- 11. Bacterial apyrase.- 12. ATP-ase from crab nerve.- 13. Myosin ATP-ase.- 14. Urease.- c) Non-specific effects of alkali metal ions.- d) Comments.- IV. Effect of alkali metal ions on mitochondria.- V. Metabolic effects on tissues and tissue slices.- a) Effects on oxygen consumption.- 1. Brain slices.- 2. Peripheral nerve.- 3. Liver slices.- 4. Muscle.- 5. Kidney slices.- 6. Isolated frog skin.- b) Effects on glycolysis.- c) Effect on acetyl choline synthesis.- d) Effect on glycogen synthesis.- e) Effects on fatty acid metabolism.- f) Effects on cellular accumulation of various substances.- g) Morphogenetic effects of lithium.- 1. The effects of lithium.- 2. Mechanism of the Li effect.- VI. Distribution of the alkali metal ions between cells and their surroundings.- a) General remarks.- b) State of potassium in living cells.- c) State of Rb and Cs in living cells.- d) State of sodium in living cells.- VII. Active and passive transport of the alkali metal ions.- A. Characterization and biological role.- a) Introduction.- b) Passive transport.- c) "Simple" passive transport.- d) The flux ratio.- e) The effect of solvent drag.- f) Passive permeability and membrane structure.- g) Permeability of intercellular cements.- h) Ionic permeability and the development of bioelectric potentials.- i) Active transport of the alkali metal ions (The "Sodium pump").- j) Relation of the active transport to metabolism.- k) Quantitative relationship between oxygen consumption and active ion transport.- 1) Temperature dependency of the "sodium pump".- m) Effects of drugs and hormones on active and passive transport.- 1. Steroid hormones.- 2. Cardiac glycosides and their aglucones.- 3. Different Hormones.- Acetyl choline.- Histamine.- Adrenaline.- Neurohypophyseal hormones.- n) Role of alkali ion transport in the regulation of the volume of living cells.- o) Mechanisms proposed for the active transport of alkali metal ions.- 1. Simple membrane-carrier transport.- 2. Electron-linked carrier transport.- 3. Propelled carrier transport.- 4. "Asymmetrically collapsing lattice" theories.- 5. The fluid circuit mechanisms.- 6. Pinocytosis.- B. Transport between cells and their surroundings.- a) Erythrocytes.- 1. Transport of potassium in human erythrocytes.- 2. Transport of sodium in human erythrocytes.- 3. Effect of pH on the Na transport.- 4. Effect of temperature.- 5. Transport of Li in human erythrocytes.- 6. Transport of Rb in human erythrocytes.- 7. Transport of Cs in human erythrocytes.- 8. Evidence for a coupling between active sodium extrusion and potassium uptake.- 9. Relation of the active and passive transports to metabolism.- 10. Effects of cardiac glucosides on the transport processes.- 11. Ion transport by red cell "ghosts".- 12. Mechanism of the active transport.- 13. Nature of the diffusion of alkali metal ions through the erythrocyte membrane.- 14. Alkali metal ion transport in other mammalian red cells.- 15. Transport of K and Na in bird red cells.- 16. Transport of K and Na in red cells of lower vertebrates.- b) Muscle.- 1. Development of the "sodium pump" concept.- 2. Net transports of K and Na in muscle.- 3. The sodium flux across the frog-muscle fibre membrane.- 4. Energy requirement of the active Na transport in frog muscle.- 5. The potassium fluxes of frog muscle.- 6. The potassium fluxes of mammalian muscle.- 7. Alkali metal ion shifts in relation to muscular activity.- c) Peripheral nerve.- 1. Movements of potassium and sodium in the resting nerve.- 2. Effect of temperature on cation fluxes in nerve.- 3. Active transport of Na in cephalopod giant axons.- 4. Coupling between Na-outflux and K-influx.- 5. Nature of the passive movement of K through the cephalopod giant axon membrane.- 6. Passive potassium transport during current flow.- 7. Passive transport of Na through the giant fibre membrane.- 8. Potassium and sodium shifts during activity.- d) Leucocytes.- e) Brain slices and isolated retina.- f) Mouse ascites carcinoma cells.- g) Liver slices.- h) Kidney cortex slices.- i) Seminal vesicle mucosa.- j) Yeast cells.- k) Ulva lactuca.- 1) Halicystis and Valonia.- m) Nitellopsis (Characeae).- n) Higher plants.- C. Transport through epithelial membranes.- a) Introduction.- b) The amphibian skin.- 1. The active sodium transport of the frog skin and its relation to the skin potential.- 2. The relation between oxygen consumption and active sodium transport.- 3. The work performed by the active sodium transport mechanism.- 4. The electromotive force of the active sodium transport.- 5. Inhibitors of the active sodium transport.- 6. Stimulants of active sodium transport.- 7. The action of neurohypophyseal hormones upon the transfer of water and salt across the frog skin.- 8. The relationship between active sodium transport and transport of water across the skin.- c) The rumen of ruminants.- d) The toad urinary bladder.- e) Intestinal mucosa.- 1. Net transport of sodium.- 2. The dependency of the sodium transport upon different factors.- 3. The unidirectional sodium fluxes.- 4. Intestinal potentials and their relation to active sodium transport.- 5. The transport of potassium across the intestinal wall.- f) Kidney tubulus.- g) The Malpighian tubules of insects.- h) The formation of the endolymph.- i) Active K transport in the formation of bull seminal plasma.- j) The gills of Eriocheir sinensis (The "woolhanded crab").- VIII. Relation of the alkali metal ions to bioelectric phenomena.- A. Relation to maintained potentials.- a) Introduction.- b) Effect of K on the resting potential of muscle and nerve.- 1. Striated muscle.- 2. Heart muscle.- 3. Smooth muscle.- 4. Nerve.- c) Dependency of the K effect upon other ion species.- d) Effect of external Na upon the resting potential of nerve and muscle.- e) Effects of the non-biological alkali metal ions upon the resting potential.- B. Relation to the electric activity of nerve and muscle.- a) The "sodium" theory of excitation (Hodgkin-Huxley-Katz).- b) The relation of the external Na concentration to the action potential of single nerve fibres.- c) Effect of Li upon the action potential of single nerve fibres.- d) Relation of K to the action potential of single nerve fibres.- e) The contributions of Na and K to the membrane current in squid axons.- f) The applicability and limitations of the sodium theory of electric activity.- g) Effect of external Na concentration upon excitation and conduction.- 1. Effects on nerve.- 2. The nerve sheath as a diffusion barrier.- 3. Effects on striated muscle.- 4. Effects on heart muscle.- h) Effect of internal Na concentration on electric activity in muscle.- i) Effects of K upon excitation and conduction.- 1. Nerve.- 2. Striated muscle.- 3. Heart muscle.- C. Relations to the electric activity of neuromuscular junctions and synapses.- a) Neuromuscular junctions.- 1. Effects of Na.- 2. Effects of potassium.- b) The sub-synaptic membrane.- D. Relation to the electric activity of electric organs.- IX. Role of the alkali metal ions in muscular contraction.- A. Introduction: Non-living models.- B. Effects on skeletal muscle.- a) Effects of Na.- b) Effects of K.- 1. Introduction.- 2. Potassium contracture.- 3. Effects of K on the mechanical response.- 4. The Fleckenstein hypothesis.- C. Effects on heart muscle.- a) Introduction.- b) Temperature and ionic effects on the heart.- c) Effects on the heart rate (the rhythm).- d) Effects upon the mechanical response of the heart.- e) The Hajdu hypothesis.- 1. The "staircase" phenomenon.- 2. Potassium ions and the development of tension.- 3. Potassium ions and contracture.- 4. Effect of Na upon the staircase.- 5. Formulation of the hypothesis.- D. Effects on smooth muscle.- a) Effect of sodium ions.- 1. Intestinal muscle.- 2. Uterus muscle.- b) Effect of potassium ions.- 1. Intestinal muscle.- 2. Uterus muscle.- 3. Vascular muscle.- Part: II The alkali metal ions in the organism.- I. Introduction.- II. Distribution of alkali metals in body compartments and tissues.- A. The sodium and potassium of the extracellular compartment (and some tissues built mainly of extracellular components).- a) Blood plasma.- b) Lymph.- c) Interstitial spaces.- d) Tendon.- e) Corium.- f) Cornea.- B. The sodium and potassium of cartilage and bone.- a) Cartilage.- b) Bone.- Amount of sodium in bone.- Nature of sodium in bone.- "Availability", function of sodium in bone.- C. The sodium and potassium of fluids contained in special extracellular cavities.- a) Synovial fluid.- b) Cerebrospinal fluid.- c) Aqueous humour.- d) Vitreous humour.- e) Endolymph, perilymph.- f) Amniotic fluid.- g) Transport over placenta.- D. The sodium and potassium of different tissues mainly composed of cells.- a) Introduction.- b) Epidermis, lens.- c) Muscular tissues.- d) Blood cells.- e) Neural tissues.- f) Glandular tissues.- g) Miscellaneous.- E. Distribution of lithium, rubidium and cesium.- Distribution of naturally occurring lithium.- Distribution of lithium after administration.- Distribution of naturally occurring rubidium.- Distribution of rubidium after administration.- Distribution of naturally occurring cesium.- Distribution of cesium after administration.- III. Total body contents of sodium and potassium. Total exchangeable sodium and potassium.- A. Total body contents.- B. Total exchangeable sodium and potassium (Nae
, Ke).- C. Relation between total body contents and total exchangeable contents.- D. Relation between isotope dilution data and data from metabolic balance studies.- E. Relation between Nae and Ke and serum concentrations.- VI. Handling of alkali metal ions by the kidney.- A. Introduction.- B. Processes involved in tubular transport of water and the predominant ions of plasma; their nature and localization.- a) The proximal tubules.- b) The distal tubular system.- Distal tubular processes concerned with water (and salt) reabsorption.- Distal reabsorption of sodium (and secretion of potassium).- Concluding remarks.- C. Transport of fluid in the nephron as a whole (relationship between glomerular and tubular factors).- D. Physical factors (pressures) affecting sodium (and water) excretion.- a) Effect of changes in the oncotic pressure of plasma.- b) Effect of changes in renal arterial pressure.- c) Effect of increase in ureteral (pelvic) pressure.- d) Effect of elevation of renal venous pressure.- e) Effects of pressures acting on the outside of the kidney.- E. Effects of changes in plasma sodium (and chloride) concentration on sodium excretion.- F. "Osmotic diuresis" and sodium (and potassium) excretion.- G. Interrelationship between urinary acidification and sodium and potassium excretion.- a) Potassium excretion as related to sodium excretion.- b) The effects of primary changes in the acid-base status of the body fluids.- Hyperventilation (respiratory alkalosis).- Increased pCO2 (respiratory acidosis).- Effects of non-respiratory ("metabolic") alkalosis on potassium excretion.- Potassium excretion in non-respiratory acidosis.- c) The effects of potassium deficiency and potassium excess.- Effects of potassium deficiency upon bicarbonate reabsorption.- Effects of administration of potassium salts (potassium excess).- d) The effects of carbonic anhydrase inhibitors.- H. Hormonal factors affecting the renal handling of sodium, potassium (and water).- a) Hormones of the adrenal cortex and other steroids.- Effects of adrenocortical insufficiency.- Natural corticosteroids.- Effects of corticoids on renal sodium and potassium excretions (and renal function in general).- Corticoid derivatives.- Licorice extract.- Progesterone.- Oestrogens.- Androgens.- b) Hormones of the adrenal medulla.- c) Hormones of the adenohypophysis.- d) Neurohypophyseal hormones.- Vasopressin (antidiuretic hormone, ADH, ?-hypophamine).- Oxytocin.- e) Hormones of the pancreas.- Insulin.- Glucagon.- f) Miscellaneous.- Renin and hypertensin.- Serotonin.- I. Effect of the renal nerves and sympathicomimetic amines on sodium and potassium excretion.- a) The renal nerves.- b) Effects of sympathomimetic amines.- J. Influence of the central nervous system on body contents and renal excretion of sodium (and water).- K. Effects of changes in the state of the cardiovascular system on sodium excretion.- a) Effects of changes in total blood volume.- b) Procedures causing redistribution of the blood volume.- c) Influence of posture.- d) Sodium retention in circulatory failure (formation of cardiac oedema).- L. Effect of exercise on renal sodium excretion.- M. Diurnal variations in the renal excretion of sodium and potassium.- N. Diuretic and natriuretic agents.- a) Introduction (definitions and types of diureses).- b) Water.- c) Osmotic diuretics.- d) Salts.- e) Acidifying diuretics.- f) Mercurial diuretics.- The typical response.- Mechanism of the renal response.- Cellular site of action.- Factors influencing the diuretic response to mercurials.- Effects of mercurials on urinary potassium excretion.- g) Xanthine diuretics.- The typical response.- The mechanism of xanthine diuresis.- h) Diuretics chemically related to xanthines.- i) Unsubstituted sulphonamides (carbonic anhydrase inhibitors).- j) Chlorothiazide (and derivatives).- k) Antialdosterones.- O. The renal excretion of lithium, rubidium and cesium.- a) Lithium.- b) Rubidium and cesium.- c) Note on thallous ions.- P. Transport of sodium and potassium across the urinary bladder wall.- V. Handling of alkali metals by exocrine glands other than the kidney.- A. The duct possessing glands.- a) Introduction.- The outward transfer of electrolytes.- The morphological site of the outward transport of electrolytes.- The reabsorption of sodium.- The morphological site of sodium reabsorption.- Glandular sodium and potassium balance during secretion.- Glandular oxygen consumption in relation to electrolyte transport.- Factors affecting sodium and potassium excretion by the duct-possessing glands 436..- Criticism of the present theory of sodium and potassium secretion.- b) The sweat glands.- Type of gland.- Rate of secretion.- Skin temperature.- Duration of secretion.- Type of stimulus.- Plasma concentration of Na und K.- Glandular blood flow.- Adaptation to salt depletion.- Adrenal cortical steroids.- Drugs.- Individual differences in sweat composition.- The secretion of Li, Cs and Rb.- The effect of prolonged sweating on the homeostasis of water, sodium and potassium.- Water loss.- Electrolyte loss.- Replacements.- The effect of sweating without replacement of water and salt.- The effect of sweating with replacement of water but not of salt.- The effect of sweating with replacement of salt but not of water loss.- c) The salivary glands.- Type of gland.- Rate of secretion.- Gland temperature.- Duration of secretion.- Type of stimulation.- Glandular blood flow.- Plasma concentration of Na and K.- Salt depletion.- Adrenal cortical steroids.- The effect of various drugs.- Individual variations.- The secretion of Li, Cs and Rb.- d) The pancreatic gland.- Rate of secretion.- Duration of secretion.- Type of stimulation.- Plasma concentration of the alkali metals.- The effect of certain drugs.- Individual variations.- e) The lacrymal gland.- Rate of secretion.- Duration of secretion.- Plasma concentration.- B. The glands of the gastrointestinal tract.- a) The oesophageal glands.- b) The gastric mucosa.- Type of gland.- Rate of secretion.- Type of stimulus.- Duration of secretion.- Plasma concentrations of Na and K (total osmolar concentration).- Mucosal blood flow and oxygen supply.- Gland temperature.- Salt depletion and adreno-cortical steroids.- Individual differences.- The secretion of lithium.- The alkali metal content of the gastric mucosa.- Mechanism of alkali metal secretion.- c) The intestinal mucosa.- Type of gland.- Rate of secretion.- Plasma concentration of the alkali metals (total osmolar concentration of the plasma).- The alkali metals in the intestine.- The mechanism of intestinal secretion.- C. The liver and the gall bladder.- a) Hepatic bile.- Collection of hepatic bile.- The electrolyte composition of hepatic bile.- Rate of secretion.- Plasma concentration of the alkali metals (total osmolar concentration of the plasma).- Hepatic blood flow and oxygen supply.- Temperature.- The excretion of lithium in the hepatic bile.- The mechanism of alkali metal excretion in the bile.- b) Gall bladder bile.- The electrolyte composition of gall bladder bile.- The reabsorptive functions of the gall bladder.- The secretory functions of the gall bladder.- c) The alkali metals in hepatic tissue.- D. The mammary gland.- E. Male organs of reproduction.- F. Female organs of reproduction.- G. The glands of the respiratory tract.- H. Concluding remarks on glandular secretion.- VI. Intestinal absorption of alkali metal ions.- A. Introduction.- B. Resins and intestinal absorption of alkali metal ions.- Properties of ion exchange resins.- The state of charging of resins present in the intestinal contents.- C. Influence of corticoids on intestinal absorption of alkali metal ions.- D. Use of resin therapy for potassium depletion.- E. Intestinal lavage as a measure to correct electrolyte imbalances.- F. Intestinal absorption as a problem in ureterocolic anastomoses.- VII. Intakes and general turnovers.- A. Intakes.- a) Contents in food components.- b) Normal intakes.- c) Diets ensuring low intakes.- B. Daily turnovers.- VIII. Effects of excesses and deficits.- A. Introduction (remarks on homeostasis).- B. Effects of sodium loading.- a) Acute.- b) Chronic.- C. Effects of potassium loading.- a) Acute.- b) Chronic.- D. Effects of lithium loading.- Gastrointestinal tract.- Muscular and nervous systems.- Circulation.- Kidneys.- Treatment of lithium intoxication.- E. Effects of rubidium loading.- a) Acute.- b) Chronic.- F. Effects of cesium loading.- a) Acute.- b) Chronic.- c) Factors influencing the excretion of cesium.- G. Sodium depletion.- a) Acute.- b) Chronic.- H. Potassium depletion.- a) Acute.- b) Chronic.- I. Function of rubidium and cesium in replacement of potassium.- J. Influence of age on the efficiency of homeostasis.- IX. Internal shifts and displacements of alkali metal ions.- A. Mobilization from or deposition in extracellular structures, especially bone.- B. Factors affecting the distribution of alkali metals between cells and extracellular fluid.- a) Hormones.- b) Excesses or deficits - primary changes in pH.- Author Index.