Preface

Ion channels are small proteins that are present in every cellular membrane. They provide the path for ions to follow their concentration gradient and thus transport stimulus or information across the membrane. When talking about ion channels, one cannot forget the counterbalance of the passive currents and maintenance of the ionic gradients mediated by ion pumps (ATPases or ion exchangers).

It is almost 100 years since the first electrical signal in a single squid giant axon was detected by Hodgkin, Huxley, and Katz. During the century, the idea of what is behind the electrical current has moved from a courageous hypothesis to a structure of an ion transporter known on the atomic level and computer simulations indicating the movement of amino acid chains during channel gating or ion pump movement.

Many types of ion channels have been observed, measured, and described since their discovery. There are ion channels so selective that they can distinguish between two small ions like Na+ and K+. In addition, there are ion channels that are permeable for molecules several times larger than ions. These channels differ in the speed of transport, the shape of conductive pores, and gating kinetics. The regulation of ion channel activity involves a broad range of mechanisms. Though the channels vary in many ways, their primary role is the same, which is the controlled passage of ions in a safe way to not disturb cellular homeostasis. Ion channels, regardless of the ion type they conduct, are often the target of medical treatment. Mutations in ion channels that affect channel activity or permeability are behind diseases such as cystic fibrosis, malignant hyperthermia, epilepsy, and many other channelopathies.

This book focuses on the tight connection between an abnormal channel or ion pump function or regulation and the diseases that emerge from these changes. The first section shows the plethora of ion channel types that are involved in pathological processes like cardiac or neurodegenerative diseases. The physiological state is a result of an interplay of many different ion channels. The slightest deviation from the "normal" of any of the small puzzle pieces can evolve into a serious condition. The second section contains chapters on a single ion transporter type and its role in different physiological and pathological states. The third section presents an example of a computer-modeled 3D channel structure that can be extremely helpful in the future of drug development.

Maintenance of the dynamic balance, that relentlessly goes on in every cell, is crucial for human health. I hope that every reader of this book, whether a student or a scientist, will find it entertaining as well as instructive.

> **Zuzana Sevcikova Tomaskova** Centre of Biosciences, Slovak Academy of Sciences, Bratislava, Slovak Republic

Section 1
