A Revolution in the Physiology of the Living Cell

398 Pages·1992·66.88 MB·English

by  Gilbert Ling

С©|/
A REVOLUTION IN
THE PHYSIOLOGY OF
THE LIVING CELL
by
Gilbert N. Ling, Ph.D.
Damadian Foundation for Basic and Cancer Research
% Fonar Corporation, Melville, New York
KRIK G K R P U B L IS H IN G CO M PA N Y
M A LA BA R , F L O R ID A
1992
Original Edition 1992
Primed and Published by
KRIEGER PUBLISHING COMPANY
KRIEGER DRIVE
MALABAR, FLORIDA 32950
Copyright © 1991 by
KRIEGER PUBLISHING COMPANY
All rights reserved. No part o f this book maybe reproduced in any form or by any meai
electronic or mechanical, including information storage and retrieval systems withe
permission in writing from the publisher.
No liability is assumed with respect to the use o f the information contained herein.
Printed in the United States o f America
Library of Congress Cataloging in Publication Data
Ling, Gilbert N.. 1919-
A revolution in the physiology o f the living cell
Gilbert L. Ling,
p. cm.
Bibliography: p.
ISBN 0-89464-398-3 (alk. paper)
I.C ell physiology. 2. Biophysics. I. Title.
Q H 63I.L562 1989
574.87— dc20 89-1101
Cl I
10 9 8 7 6 5 4 3 2
То
Raymond and Donna Damadian
CONTENTS
A Short History and Acknowledgments xi
Introduction xxi
Chapter I. Early Theories of the Living Cell 1
1.1. Life and Death of a Living Cell I
1.2. The Cell Theory and the Protopasmic Doctrine 2
1.2.1. Gelatin as a Model of Protoplasm 3
1.2.2. Copper Ferrocyanide Gel as a Model of Plasma 3
Membrane
1.3. The Membrane Theory 4
1.4. The Protoplasmic Theory and Colloid Chemistry 6
Chapter 2. The Membrane-Pump Theory 9
2.1. The Origin of the Membrane-Pump Hypothesis 9
2.2. 'The Excessive Energy Need of the Na Pump; A Decisive 10
Disproof
2.2.1. The Effects of Metabolic Inhibition on Cell Na+ 10
2.2.2. The Original Calculations Comparing the Minimum 12
Energy Need of the Postulated Na Pump with the
Maximum Available Energy
2.2.3. Gross Underestimation of the Disparity Between 15
Miximum Available and Minimum Needed Energy
for the Na Pump
2.2.4. Remedial Postulations to Reduce the Energy Need 16
of the Na Pump
2.2.5 Many More Pumps Required at the Plasma 17
Membrane
2.2.6. Still More Pumps Required at the Membranes of 19
Su heel In la r Particles
2.3. The Failure to Demostrate Pumping of K+ and Na+ 20
Against Concentration Gradients in an Ideal Cytoplasm-
Free Membrane-Sac Preparation
2.4. Evidence Once Considered to Strongly Support the 20
Membrane-Pump Hypothesis Shown to lx? Erroneous or
Equivocal
2.4.1. Intracellular K+ Mobility 20
2.4.2. Intracellular K+ Activity 21
2.4.3. The Intracellular “Reference Phase” Studies 22
2.4.4. Active Transports in Hollow Membrane Sacs or 22
Vesicles
2.5. Summary 28
VI
CONTENTS vii
Chapter 3. The Living State 31
3.1. The Story of the Living Cell: Л System of Protein- 31
Water-K+ Interacting with an Environment of Water and
Na+
3.2. A Discrete High-(Negative)-Energy, L,ow-Entropy State 31
Called the Living Stale
3.3 A Diagram of the Living Cell 33
Chapter 4. Cell Potassium 39
4.1. Enhanced Counterion Association withC harge-fixation 39
4.2. Stoichiometric Na+ (and K+) Adsorption on Protein /3- 41
and y-Carboxyl Groups in Vitro
4.3. Demonstration of a StoichiometricR elation Between 44
Concentration of Cell K+ and the Concentration of
Cytoplasmic Proteins, Primarily Hemoglobin
4.4. Adsorption of Cell K+ on /3- and y-Carboxyl Groups of 45
Cytoplasmic Proteins
4.4.1. Localized Distribution of K+ in Cell Regions rich in 45
/3- and y-Carboxyl Groups
4.4.2. The Selectivity in Adsorption Among Tl+, Cs+ and 50
Other Ions Not Due to Functional Cell Membrane
and Postulated Pumps
4.4.3. Demonstration of Specific Adsorption of Alkali- 61
Metal Ions on the /3- and y-Carboxyl Groups Inside
Living Cells
4.4.4. Evidence that in Living Muscle Cells /3- and y- 62
Carboxyl Groups Carried by Myosin and Maintained
at the Resting Living State Selectively Adsorb K+
Over Na+.
4.4.5. Summary 65
Chapter 5. Cell Water 69
5.1. The Physics of Multilayer Adsorption of Water 69
5.2. The Polarized Multilayer Theory of Cell Water and 71
Results of Experimentral lesting
5.2.1. Background 71
5.2.2. The Polarized-Multilayer (PM) Theory of Cell Water 73
5.2.3. The Subsidiary Hypothesis of Solute Exclusion 77
5.2.4. Predictions of the Polarized-Multilayer (PM) Theory HO
5.2.5. Results of Experimental Testing of the Predictions 81
of the PM Theory
5.3 Summary 106
Chapter 6. Induction 111
6.1. The Inductive Effect in the Properites and Behaviors of 112
Small Organic Molecules
6.2. The Inductive Effect in the Properties and Behaviors of 116
Proteins
viii CONTENTS
6.2.1. Inductive Effect on Protein Conformation and 118
Water Polarization
6.2.2. Inductive Effect on the Reactivity of Side-Chain SH 121
Groups
6.2.3. Inductive Effect on the Fluorescence of Tyrosine 123
and Tryptophane Residues
6.2.4 Inductive Effect on the Rank Order of Selective Ion 125
Adsorption on (3- and y-Carboxyl Groups
6.3. Summary 130
Chapter 7. Coherent Behavior and Control Mechanisms 135
7.1. Theory of Cooperative Adsorption (the Yang-Ling 136
Cooperative Adsorption Isotherm)
7.2. Experimental Findings in Harmony with the T heory of 140
Spontaneous Autocooperative T ransition
7.2.1. Cooperative Interaction Among Backbone NHCO 140
Sites
7.2.2. Cooperative Interaction Among (3- and y- Carboxyl 141
Groups
7.3. Theory of the Control of Transition Between Discrete 142
Cooperative States by Cardinal Adsorbents
7.3.1. A Sketch of the Basic Concepts 142
7.3.2. The Definition and Classification of Cardinal 144
Adsorbents
7.3.3. A Model Demonstrating How a Cardinal Adsorbent 145
May Initiate and Maintain an All-or-None Change
of a Protein System
7.4. Experimental Findings in Harmony with the T heory of 149
Controlled Autocooperative Transition
7.4.1. Allosteric Control by Acid of the Shift Between 149
Water Binding to Urea Binding on Bovine Serum
Albumin
7.4.2. Zipper-Like Unmasking of Carboxyl Groups in 150
Response to Acid Binding onto “Trigger Groups” on
Ferri- and Carboxyhemoglobin
7.4.3. In Vitro Allosteric Control of Cooperative Binding 152
of Oxygen on Hemoglobin by 2,3-DPG, 1HP, and
ATP
7.5. Summary 155
Chapter 8. Solute Distribution 159
8.1. Solute Distribution in living Cells 160
8.1.1. Solute Primarily in Cell Water 162
8.1.2. Solute in Cell Water and on Adsorption Sites 162
8.1.3. Solute Primarily on Adsorption Sites 166
8.2 Cooperativity in Adsorption in Living Cells 169
8.3 Control of Cooperative Adsorption and Transition 171
8.3.1. Control by Ca+ f 171
8.3.2. Control By Ouabain 172
CONTENTS ix
8.3.3. The Indifference of the «/-values of Large Solutes in 177
Cell Water after Exposure to Insulin, Ouabain and
Other Secondary' Cardinal Adsorbents
8.4. The Role of ATP in Maintenance of the Living State 178
and in Work Performance
8.4.1. ATP as a Reservoir of Utilizable Energy: the 179
Attractive but Incorrect High Energy Phosphate
Bond Concept
8.4.2. ATP as the Prime Living-State-Conserving Cardinal 179
Adsorbent and its Role in W'ork Performance
8.4.3. Experimental Confirmation of Some Predictions of 187
the Theory
8.4.4. In-Vitro Demonstration of the Maintenance of the 197
Living State by ATP (and Its “Helpers”)
8.5 Summary 198
Chapter 9. Permeability to Water, Ions, Nonelectrolytes. and 205
Macro molecules
9.1. The l.ipoidal Membrane Model in the Past and the 206
Present
9.1.1. Overton’s Original Model 206
9.1.2. Subsequent Modifications of the Overton Model 206
9.1.3 Overton’s Lipid-Layer Model Once Again 208
9.2. The Cell Membrane as a Lipid-Protein-Polarized- Water 212
System
9.2.1. Permeability to Water and Nonelectroly tes 213
9.2.2. Permeability to Ions and its Control 230
9.3. Summary 244
Chapter 10. Cell Volume and Shape 249
10.1. Cell Volume Maintenance and Regulation According to 249
Traditional Hypothesis
10.2 Cell Volume Maintenance and Regulation According to 253
the AI Hypothesis
10.2.1. A New Theory of Cell-Volume Maintenance 253
10.2.2. The Restraining Effect of Intracellular Salt 259
Linkages in the Maintenance of Cell Volume, and
Specific Swelling Ef fects of Some Electrolytes
10.2.3. Cytoplasmic Proteins and their Conformation in 263
the Determination and control of Cell Shape
10.2.4. I’he Role of ATP in the Control of Cell Volume 265
10.2.5. The Role of ATP in the Control of (ell Shape 268
10.3 Summary 271
Chapter II. Cellular Electrical Potentials 273
11.1. Bernsteins Membrane Theory of Resting and Action 273
Potentials
11.2. The Ionic Theory of Resting and Action Potential of 275
Hodgkin and Katz
X CONTENT
11.2.1. Theory 27
11.2.2. Results of Experimental'lesiing 27'
11.2.3 Modifications of Theory 27
11.2.4. Decisive Evidence Against Both the Original Ionic 27'
Theory and its Modifications
11.3. The Surface-Adsorption (SA) Theory of Cellular 28'
Resting and Action Potential
11.3.1. Theory 28*
1 1.3.2. Results of Experimental Testing 281
11.4. Control of the Resting Potential According to SA 28!
Theory
11.4.1. Theory 28!
11.4.2. Results of Experimental Testing of Theory and 29*
Other Related Observations
11.5 Action Potential According to Hodgkin-Huxley and 29!
According to A1 Hypothesis
11.5.1. The Hodgkin-Huxley Analyses and Interpretation 29!
of the Action Potential
1 1.5.2. Action Potential According to the A1 Hypothesis 30!
and Experimental Findings in Harmony with the
Theory
11.6. Summary 31!
Chapter 12. The Completion of a Scientific Revolution and 3H
Events Beyond
12.1. Definitions of “Scientific Revolution” 31 f
12.2. A Unique Feature of the Scientific Method as Applied 32(
to Cell Physiology
12.3. Outlines of Old and New Theory 32(
12.3.1. The Membrane-Pump Theory 32(
12.3.2. The Association-Induction (AI) Hypothesis 321
12.4 Results of Testing of Theoretical Postulates on 32S
Inanimate Models
12.5 The Fulfillment of All the Required Criteria for the 324
Completion of a Scientific Revolution
12.0 Outstanding Features of a Valid New Theory 33S
12.6.1. Expanding Coverage 33(:
12.6.2. Simplicity in Governing Rules 33(:
12.6.3. Predicting New Relations 336
12.7. The Future 339
References 3 4 1
Index 35/
X CONTENTS
11.2.1. Theory 275
11.2.2. Results of Experimental Testing 276
11.2.3 Modifications o f Theory 277
11.2.4. Decisive Evidence Against Both the Original Ionic 279
Theory and its Modifications
11.3. The Surface-Adsorption (SA) Theory of Cellular 280
Resting and Action Potential
11.3.1. Theory 280
11.3.2. Results of Experimental Testing 282
11.4. Control of the Resting Potential According to SA 289
Theory
11.4.1. Theory 289
11.4.2. Results of Experimental Testing of Theory and 290
Other Related Observations
11.5 Action Potential According to Hodgkin-Huxley and 299
According to A1 Hypothesis
11.5.1. The Hodgkin-Huxley Analyses and Interpretation 299
of the Action Potential
11.5.2. Action Potential According to the Al Hypothesis 303
and Experimental Findings in Harmony with the
Theory
11.6. Summary 312
Chapter 12. The Completion of a Scientific Revolution and 319
Events Beyond
12.1. Definitions of “Scientific Revolution” 319
12.2. A Unique Feature of the Scientific Method as Applied 320
to Cell Physiology
12.3. Outlines o f Old and New Theory 320
12.3.1. The Membrane-Pump Theory 320
12.3.2. The Association-Induction (Al) Hypothesis 321
12.4 Results of Testing of Theoretical Postulates on 322
Inanimate Models
12.5 The Fulfillment of All the Required Criteriaf or the 324
Completion of a Scientific Revolution
12.6 Outstanding Features of a Valid New Theory 335
12.6.1. Expanding Coverage 336
12.6.2. Simplicity in Governing Rules 336
12.6.3. Predicting New Relations 336
12.7. The Future 339
References 341
Index 557