The Paracellular Channel

Biology, Physiology, and Disease

Jianghui Hou

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128146361
• Topic: Biological Sciences
• Subtopic: Biophysics
• Index: Biological Sciences

The Paracellular Channel: Biology, Physiology and Disease serves as the first volume to offer a cohesive and unifying picture of the critical functions of paracellular channels (tight junctions) in different tissues. This new class of ion channel utilizes a completely different mechanism to create ion passage pathways across the cell junction. This volume outlines common principles that govern the organization and regulation of these diverse cellular structures, describes the methodology of study, and highlights the pathophysiologic consequence of abnormal structure and functions of the paracellular channels in human diseases.

Coverage includes biochemical, biophysical, structural, physiologic analyses of the paracellular channel, and new technologies for recording and characterization.

• Offers integrated coverage of all key aspects of the paracellular channel, an understudied field that may hold key insights into some of the most mysterious aspects of physiology
• Targets different levels of expertise, spanning from graduate students, interns and clinical fellows, to seasoned researchers that study functions, regulation and dysfunctions of different tissue barriers
• Provides a cohesive and unifying picture that describes the critical functions of paracellular channels (tight junctions) in different tissues

Chapter 1

Introduction

Abstract

The paracellular channel is a new concept in ion channel biology. Its structure and function are vastly different from the membrane channel. The paracellular channel is located within the tight junction. Several key milestones in paracellular channel biology are recounted, including the discovery of its molecular component, the establishment of its connection to human disease, the elucidation of its assembling mechanism, the resolution of its crystal structure, the separation of its water from ion permeability, and the development of its recording approach. The paracellular channel is being recognized as an essential component of the cellular transport machinery that evolves to cope with various transport needs.

Keywords

crystal structure

electrophysiology

genetic disease

ion channel

mutation

protein interaction

tight junction

water channel

1.1 A new class of ion channel

The cell membrane is a biologic lipid bilayer that separates the interior of the cell from the exterior environment. Ion channels are pore forming membrane proteins that allow passage of ions through the cell membrane (Fig. 1.1). When life evolves from unicellular to multicellular organisms, coordination of cell growth by a process known as morphogenesis creates complex three-dimensional structures, such as the blood vessel, renal tubule, pulmonary alveolus, and so on. These tissue structures, made of continuous layers of cells, separate the exterior environment into two independent compartments. The paracellular channel is a new class of ion channel oriented perpendicular to the plasma membrane plane and serving to join the two exterior compartments (Fig. 1.2). The paracellular channel, now believed to be made of the class of claudin proteins, conducts ions in a similar way to the conventional membrane channel by displaying size and charge selectivity (Tang & Goodenough, 2003; Tsukita & Furuse, 2000). However, the paracellular channel is fundamentally different from the membrane channel in many aspects.

Figure 1.1 Membrane ion channel.
The ion channel in the lipid bilayer permits passage of potassium ions (labeled in violet) but not sodium ions. The oxygen atoms (labeled in red) of the amino acid residues forming the channel pore interact with and stabilize the potassium ions by creating an environment very similar to the aqueous environment outside the lipid bilayer. Cells may open or close the channel by employing additional gating mechanisms. The depicted ion channel structure is based upon the X-ray analysis of the KcsA K⁺ channel from Streptomyces lividans (MacKinnon, 2004).

Figure 1.2 Paracellular ion channel.
The paracellular channel is found within the TJ structure and is part of the paracellular diffusion barrier between the two plasma membranes. The paracellular channel conducts ions on the basis of size and charge. The paracellular channel is thought ...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• Dedication
• Author Biography
• Preface
• Acknowledgment
• Chapter 1: Introduction
• Chapter 2: Paracellular Channel Formation
• Chapter 3: Paracellular Channel Recording
• Chapter 4: Paracellular Cation Channel
• Chapter 5: Paracellular Anion Channel
• Chapter 6: Paracellular Water Channel
• Chapter 7: Paracellular Channel in Organ System
• Chapter 8: Paracellular Channel in Human Disease
• Chapter 9: Paracellular Channel as Drug Target
• Chapter 10: Paracellular Channel Evolution
• Chapter 11: Perspective
• Index