Ion Channel Kinetics: A conceptual approach

Scientists have tended to approach the study of electricity, or excitability, within biological systems empirically and, by extension, biology has therefore fragmented into myriad domains, each with its own lore and wisdom. As electrophysiology is a province within the realm of biophysics, the subject has traditionally been approached from a mathematical standpoint, often at the expense of a more holistic approach to understanding the nature of biological systems. To this extent, we need to be careful that our theoretical abstraction from the biological context, and our use of tools which are invariably prone to artifacts, do not disrupt or distort the very essence of what we are seeking to understand. We should, therefore, avoid the pitfalls of failing to understand the nature of living systems and of falling prey to the absolutism of physics, a paradigm of scientific thought which tends to refute measurements or findings simply because we cannot explain them theoretically or model them mathematically. The field of biophysics encompasses the disciplines of biochemistry, electronics, optics, physics, mathematics, physiology, genetics, physiology, and pharmacology. It is, therefore, an advanced field, one which is seldom encountered as an undergraduate. This should not, however, preclude us from attempting to explain the fundamentals of electrophysiology in broader, more conceptual terms, rather than spinning an opaque web of mathematical intricacy and complexity. It is in this spirit that we shall introduce the intriguing world of ion channels, avoiding a rigid use of mathematics and religiously deriving innumerable equations from first principles (as this has been done already). Throughout this work, we shall introduce key concepts progressively, crossing each bridge in turn as we come to it. Yet Einstein's laws of relativity and Newton's laws of motion are as beautiful as they are penetrating. The insights they provide are simple, yet powerful. Within a few symbols, they impart a greater understanding of the natural world than could be gleaned from a thousand words of descriptive narrative. Thus, an equation serves as a wondrous dynamic equilibrium whose symbols come to predictive life. This book will seek to approach an understanding of ion channels in the same vein, using those practical problems which I have been privileged to solve from first principles. However, the use of mathematics throughout this work has been sparing, as we cannot hope to understand the living, breathing cycles and patterns of nature through cold-minded abstraction and reductionism. Finally, these biophysical solutions are then placed into their biomedical context within the appendices so that their greater significance is not lost.