Cellular and Molecular Physiology of Cell Volume Regulation

Kevin Strange

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781000722086
• Edition: 1
• Topic: Scienze biologiche
• Subtopic: Biologia cellulare

The ability to regulate cell volume in the face of osmotic challenge is one of the most fundamental of cellular homeostatic mechanisms. Cellular and Molecular Physiology of Cell Volume Regulation is an integrated collection of articles describing key aspects of cell volume control. The book has been organized around concepts and cellular/molecular processes rather than around mechanisms of volume regulation in specific cell types in order to make it more accessible to a multidisciplinary audience of students, instructors, and researchers.

Part I

Fundamental Principles and Physiological Roles of Cell Volume Regulation

Chapter 1

Principles of Cell Volume Regulation

Kenneth R. Hallows and Philip A. Knauf

TABLE OF CONTENTS

I.	Introduction
II.	Equilibrium and Transport of Water Across Cell Membranes A. Structure and Behavior of Intracellular Water B. Fundamental Equilibrium Relations C. Water Equilibrium and Osmotic Phenomena 1. Relationship of Osmotic Pressure to Solute Concentration 2. Corrections for Nonideal Behavior 3. Implications of Osmotic Equilibrium D. Water Transport: Definitions and Equations E. Mechanisms of Water Transport Across Cell Membranes
III.	Equilibrium and Transport of Solutes Across Cell Membranes A. Nemst Potential and Donnan Equilibrium B. Nature of the Transport Pathways (Pumps and Leaks) 1. Cellular Pumps 2. Cellular Leaks a. Channels b. Diffusive Ion Flux Equations and Their Uses c. Coupled Transport d. Equilibrium vs. Kinetics of Coupled Transport
IV.	Animal Cell Volume Regulation A. General Principles — Cellular Accounting B. Chronic Volume Regulation C. Acute Volume Regulation 1. Background and Description a. Significance b. Classifications c. Volume-Regulatory Transport Systems 2. Analysis of Volume-Regulatory Processes a. Difference between Primary and Secondary R VI b. Sensor-Transducer-Effector Systems in Volume Regulation c. Coordination of Volume-Regulatory Transport Processes d. Identification of Rate-Limiting Processes e. Phenomenological Effects of Volume-Regulatory Fluxes f. Complicating Effects of Volume-Regulatory Fluxes
V.	Relationship of Volume Regulation to Cellular Physiology

References

I. INTRODUCTION

Early studies of osmotic phenomena investigated nonidealities in the volume changes of cells exposed to anisotonic conditions. In the 1930s and 1940s, Ponder and others observed that hypotonically swollen red cells do not always behave as “perfect osmometers”.^1,2 Rather, they often swell less in hypotonic media than expected if water exchange alone were involved. Among other possible explanations, it was postulated that these cells could be losing osmotically active solutes to the surrounding media under hypotonic conditions. Although this hypothesis has since been borne out, additional factors also contribute to the nonideal osmotic behavior of red cells, such as concentration-dependent changes in the osmotic coefficient of hemoglobin.^{3, 4, 5}

It has long been recognized that in animal cells, which lack rigid cell walls and thus cannot support substantial pressure gradients across the cell membrane, the control of cell volume is achieved through the regulation of intracellular solute content. The pump-and-leak concept for the long-term or chronic maintenance of cell volume was first formulated by Davson and Dean (1940)⁶ and later developed quantitatively by Leaf (1959),⁷ Ussing (1960),⁸ and Tosteson and Hoffmann (1960).⁹ In this model, cell volume control represents a balance between active ion pumps (e.g., the Na^+, K⁺-ATPase) and passive “leak” fluxes to maintain a steady state. In recent years, it has been discovered that these leaks or downhill flows of ions often represent very sophisticated and highly regulated transport systems, such as coupled cotransporters and exchangers and regulated ion channels.¹⁰ Kregenow was among the first to investigate the ionic bases of short-term volume-regulatory responses in animal cells in his evaluation of the responses of duck erythrocytes to hypotonic and hypertonic media.^11,12 Since then, the capacity for anisotonic volume regulation has been observed in many cell types (for recent reviews see References 10 and 13, 14, 15, 16). Today, volume regulation research has branched out to involve many disciplines, from ion transport and electrophysiological studies to cellular signaling and molecular genetics.

The rest of this chapter will consider in detail: (1) the behavior of water and solutes in cells and the basis for their equilibrium and transport across cell membranes, and (2) the general principles, processes, and phenomena involved in the control of animal cell volume under both steady-state and anisotonic conditions.

II. EQUILIBRIUM AND TRANSPORT OF WATER ACROSS CELL MEMBRANES

A. STRUCTURE AND BEHAVIOR OF INTRACELLULAR WATER

Before embarking on a quantitative analysis of the equilibrium and transport properties of water across cell membranes, one should consider the extent to which it is expected to behave in an “ideal” manner from a fundamental thermodynamic standpoint. Specifically, it is known that sufficiently near to a surface, water behaves as if it is immobilized or bound to the surface, with diminished activity and solvent properties.¹⁷ The proportion of such “nonideal” intracellular water to total cell water has been the subject of some debate.

Shporer and Civan’s nuclear magnetic resonance data provided evidence that only a small portion (~5%) of cellular water behaves as if it were bound.¹⁸ This would correspond only to water in the first one or two layers of molecules next to cell surfaces.

Clegg,¹⁹ however, argues that a large fraction of total cell water exhibits properties markedly different from that of bulk water. To support this hypothesis, he cites the findings of Kempner and Miller that the composition and metabolic activities of the cytosol (obtained by methods of cell disruption and fractionation) bear almost no resemblance to those of the aqueous cytoplasm of intact cells.^20,21 Furthermore, measurements of long-range forces between surfaces suggest that the influence of surfaces (e.g., phospholipid bilayers and the cytoskeleton) on water may extend over distances as large as 50 Å (17 molecular layers of water).^22,23 This could have profound effects on the kinetics of enzymes in the cytoplasm. For example, the viscosity of aqueous microenvironments adjacent to enzymes may play a key role in rate enhancement. Indeed, certain microenvironments can cause the association or crowding of proteins. The effect of macromolecular crowding on intracellular solute association may play a key role in the signaling pathway for the activation of volume-regulatory responses (discussed below; see also Chapter 10).

Although a significant fraction of cell water may indeed have altered properties, osmotic experiments provide little evidence t...