A Revolution in the Physiology
of the Living Cell

Gilbert N. Ling, Ph.D.

Damadian Foundation for Basic and Cancer Research
c/o Fonar Corporation, Melville, New York

ISBN 0-89464-398-3
Full text [PDF]


A Short History and Acknowledgments

Chapter 1. Early Theories of the Living Cell
1.1. Life and Death of a Living Cell
1.2. The Cell Theory and the Protoplasmic Doctrine
  1.2.1. Gelatin as a Model of Protoplasm
1.2.2. Copper Ferrocyanide Gel as a Model of Plasma Membrane
1.3. The Membrane Theory
1.4. The Protoplasmic Theory and Colloid Chemistry
Chapter 2. The Membrane-Pump Theory
2.1. The Origin of the Membrane-Pump Hypothesis
2.2. The Excessive Energy Need of the Na Pump; A Decisive Disproof
  2.2.1. The Effects of Metabolic Inhibition on Cell Na+
2.2.2. The Original Calculations Comparing the Minimum Energy Need
of the Postulated Na Pump with the Maximum Available Energy
2.2.3. Gross Underestimation of the Disparity Between Maximum
Available and Minimum Needed Energy for the Na Pump
2.2.4. Remedial Postulations to Reduce the Energy Need of the Na Pump
2.2.5. Many More Pumps Required at the Plasma Membrane
2.2.6. Still More Pumps Required at the Membranes of Subcellular Particles
2.3. The Failure to Demonstrate Pumping of K+ and Na+ Against Concentration
Gradients in an Ideal Cytoplasm-Free Membrane-Sac Preparation
2.4. Evidence Once Considered to Strongly Support the Membrane-Pump Hypothesis
Shown to be Erroneous or Equivocal
  2.4.1. Intracellular K+ Mobility
2.4.2. Intracellular K+ Activity
2.4.3. The Intracellular "Reference Phase" Studies
2.4.4. Active Transports in Hollow Membrane Sacs or Vesicles
2.5. Summary
Chapter 3. The Living State
3.1. The Story of the Living Cell: A System of Protein-Water-K+ Interacting with
an Environment of Water and Na+
3.2. A Discrete High-(Negative)-Energy, Low-Entropy State Called the Living State
3.3. A Diagram of the Living Cell
Chapter 4. Cell Potassium
4.1. Enhanced Counterion Association with Charge-fixation
4.2. Stoichiometric Na+ (and K+) Adsorption on Protein beta- and gamma-Carboxyl
Groups in Vitro
4.3. Demonstration of a Stoichiometric Relation Between Concentration of Cell K+
and the Concentration of Cytoplasmic Proteins, Primarily Hemoglobin
4.4. Adsorption of Cell K+ on beta- and gamma-Carboxyl Groups of Cytoplasmic
  4.4.1. Localized Distribution of K+ in Cell Regions rich in beta- and gamma-Carboxyl
4.4.2. The Selectivity in Adsorption Among Tl+, Cs+ and Other Ions Not Due to
Functional Cell Membrane and Postulated Pumps
4.4.3. Demonstration of Specific Adsorption of Alkali-Metal Ions on the beta- and
gamma-Carboxyl Groups Inside Living Cells
4.4.4. Evidence that in Living Muscle Cells beta- and gamma-Carboxyl Groups
Carried by Myosin and Maintained at the Resting Living State Selectively Adsorb K+
Over Na+
4.4.5. Summary
Chapter 5. Cell Water
5.1. The Physics of Multilayer Adsorption of Water
5.2. The Polarized Multilayer Theory of Cell Water and Results of Experimental
  5.2.1. Background
5.2.2. The Polarized-Multilayer (PM) Theory of Cell Water
5.2.3. The Subsidiary Hypothesis of Solute Exclusion
5.2.4. Predictions of the Polarized-Multilayer (PM) Theory
5.2.5. Results of Experimental Testing of the Predictions of the PM Theory
5.3 Summary
Chapter 6. Induction
6.1. The Inductive Effect in the Properties and Behaviors of Small Organic Molecules
6.2. The Inductive Effect in the Properties and Behaviors of Proteins
  6.2.1. Inductive Effect on Protein Conformation and Water Polarization
6.2.2. Inductive Effect on the Reactivity of Side-Chain SH Groups
6.2.3. Inductive Effect on the Fluorescence of Tyrosine and Tryptophane Residues
6.2.4 Inductive Effect on the Rank Order of Selective Ion Adsorption on beta- and
gamma-Carboxyl Groups
6.3. Summary
Chapter 7. Coherent Behavior and Control Mechanisms
7.1. Theory of Cooperative Adsorption (the Yang-Ling Cooperative Adsorption
7.2. Experimental Findings in Harmony with the Theory of Spontaneous
Autocooperative Transition
  7.2.1. Cooperative Interaction Among Backbone NHCO Sites
7.2.2. Cooperative Interaction Among beta- and gamma-Carboxyl Groups
7.3. Theory of the Control of Transition Between Discrete Cooperative States by
Cardinal Adsorbents
  7.3.1. A Sketch of the Basic Concepts
7.3.2. The Definition and Classification of Cardinal Adsorbents
7.3.3. A Model Demonstrating How a Cardinal Adsorbent May Initiate and
Maintain an All-or-None Change of a Protein System
7.4. Experimental Findings in Harmony with the Theory of Controlled
Autocooperative Transition
  7.4.1. Allosteric Control by Acid of the Shift Between Water Binding to Urea
Binding on Bovine Serum Albumin
7.4.2. Zipper-Like Unmasking of Carboxyl Groups in Response to Acid Binding
onto "Trigger Groups" on Ferri- and Carboxyhemoglobin
7.4.3. In Vitro Allosteric Control of Cooperative Binding of Oxygen on
Hemoglobin by 2,3-DPG, IHP, and ATP
7.5. Summary
Chapter 8. Solute Distribution
8.1. Solute Distribution in Living Cells
  8.1.1. Solute Primarily in Cell Water
8.1.2. Solute in Cell Water and on Adsorption Sites
8.1.3. Solute Primarily on Adsorption Sites
8.2. Cooperativity in Adsorption in Living Cells
8.3. Control of Cooperative Adsorption and Transition
  8.3.1. Control by Ca++
8.3.2. Control By Ouabain
8.3.3. The Indifference of the q-values of Large Solutes in Cell Water after
Exposure to Insulin, Ouabain and Other Secondary Cardinal Adsorbents
8.4. The Role of ATP in Maintenance of the Living State and in Work Performance
  8.4.1. ATP as a Reservoir of Utilizable Energy: the Attractive but Incorrect
High Energy Phosphate Bond Concept
8.4.2. ATP as the Prime Living-State-Conserving Cardinal Adsorbent and its Role
in Work Performance
8.4.3. Experimental Confirmation of Some Predictions of the Theory
8.4.4. In-Vitro Demonstration of the Maintenance of the Living State by ATP
(and Its "Helpers")
8.5. Summary
Chapter 9. Permeability to Water, Ions, Nonelectrolytes,
and Macromolecules
9.1. The Lipoidal Membrane Model in the Past and the Present
  9.1.1. Overton's Original Model
9.1.2. Subsequent Modifications of the Overton Model
9.1.3 Overton's Lipid-Layer Model Once Again
9.2. The Cell Membrane as a Lipid-Protein-Polarized-Water System
  9.2.1. Permeability to Water and Nonelectrolytes
9.2.2. Permeability to Ions and its Control
9.3. Summary
Chapter 10. Cell Volume and Shape
10.1. Cell Volume Maintenance and Regulation According to Traditional Hypothesis
10.2. Cell Volume Maintenance and Regulation According to the AI Hypothesis
  10.2.1. A New Theory of Cell-Volume Maintenance
10.2.2. The Restraining Effect of Intracellular Salt Linkages in the Maintenance
of Cell Volume, and Specific Swelling Effects of Some Electrolytes
10.2.3. Cytoplasmic Proteins and their Conformation in the Determination and
control of Cell Shape
10.2.4. The Role of ATP in the Control of Cell Volume
10.2.5. The Role of ATP in the Control of Cell Shape
10.3 Summary
Chapter 11. Cellular Electrical Potentials
11.1. Bernsleins Membrane Theory of Resting and Action Potentials
11.2. The Ionic Theory of Resting and Action Potential of Hodgkin and Katz
  11.2.1. Theory
11.2.2. Results of Experimental Testing
11.2.3 Modifications of Theory
11.2.4. Decisive Evidence Against Both the Original Ionic Theory and its
11.3. The Surface-Adsorption (SA) Theory of Cellular Resting and Action Potential
  11.3.1. Theory
11.3.2. Results of Experimental Testing
11.4. Control of the Resting Potential According to SA Theory
  11.4.1. Theory
11.4.2. Results of Experimental Testing of Theory and Other Related Observations
11.5. Action Potential According to Hodgkin-Huxley and According to AI Hypothesis
  11.5.1. The Hodgkin-Huxley Analyses and Interpretation of the Action Potential
11.5.2. Action Potential According to the AI Hypothesisand Experimental
Findings in Harmony with the Theory
11.6. Summary
Chapter 12. The Completion of a Scientific Revolution and
Events Beyond
12.1. Definitions of "Scientific Revolution"
12.2. A Unique Feature of the Scientific Method as Applied to Cell Physiology
12.3. Outlines of Old and New Theory
  12.3.1. The Membrane-Pump Theory
12.3.2. The Association-Induction (AI) Hypothesis
12.4. Results of Testing of Theoretical Postulates on Inanimate Models
12.5. The Fulfillment of All the Required Criteria for the Completion of a Scientific Revolution
12.6. Outstanding Features of a Valid New Theory
  12.6.1. Expanding Coverage
12.6.2. Simplicity in Governing Rules
12.6.3. Predicting New Relations
12.7. The Future

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