Chapter 1 - Introduction

Abstract

Ion transport in and out of the cell across the surface membrane, or among different intracellular compartments are mediated by membrane proteins known as “ion channels,” pumps, and transporters. This book focuses on the first group of proteins. Ion channels are considered to be gated pores whose opening and closing may be intrinsic or regulated. Mutations in the promoter region of an ion channel gene may cause underexpression or overexpression of the channel protein. Moreover, mutations in the coding region of ion channel genes may lead to the gain or loss of channel function, either of which may have deleterious consequences. Mutations that cause reduced channel activity give rise to pseudohypoaldosteronism. Some diseases result from defective regulation of channel activity by intracellular or extracellular ligands or modulators. This can be due to the mutations in the genetic encoding of the regulatory molecules themselves, or because of defects in the pathways leading to their production. This is the case for some forms of diabetes mellitus. Auto antibodies to channel proteins may produce disease either by down regulating or by enhancing channel function. Ion channels may act as lethal agents, being secreted by cells and inserting into the membrane of a target cell to form large nonselective pores that cause cell lysis and death. Complement and the haemolytic toxin produced by the bacterium Staphylococcus aureus are examples of this type of ion channel. The chapter concludes by describing ion channels that are targets for a large and diverse group of toxins that mediate their effects enhancing or inhibiting channel function. The high-affinity and specificity of these toxins have led to their use as ligands for the purification of ion channel proteins. For example, mutations in three different genes give rise to LQT syndrome, a relatively rare cardiac disorder that causes sudden death from ventricular arrhythmia in young people. Conversely, different mutations in the same gene may result in very different clinical phenotypes. The frequency of most channelopathies in the general population is very low, as is the case with all single gene disorders. However, the insight they have given into the relationship between ion channel structure and function, and into the physiological role of the different ion channels, has been invaluable.