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The fee code for users of the Transactional Reporting Service is: [1-58829-698-9/07 $30]. Printed in the United States of America. 10987654321 eISBN 978-1-59745-529-9 Library of Congress Control Number: 2007931074 Preface Patch-clamp electrophysiology became commonly used since its development by Bert Sakmann and Erwin Neher in 1981. The past two decades brought major advances not only in the patch-clamp technique but in the method’s extensive applications to solve diverse scientific problems. In addition to an increase in the number of people utilizing this technique, there has been a tremendous improvement in the range of sophisticated equipment, elevating this method from the level of “wizardry” to routine usage. Recently, with the emergence of automated/parallel patch clamp, a major reorganization has taken place in the pharmacological applications of this methodology. The goal in this volume was to summarize the typical patch-clamp appli- cations and to assist scientists in identifying problems, which could be best addressed by this technique. In addition, this volume will provide the step-by-step procedures to perform the experiments that will answer those questions. The experiments described in this book will require a basic level of electrophysiological training. Our intention was not to teach the reader patch- clamp instrumentation and technique, as several basic and advanced level books have already been published, but to help an experimenter safely and effec- tively venture into new areas of electrophysiology and to routinely use the patch-clamp technique to answer scientific questions. To enhance the enthusiasm of non-electrophysiologists toward this method, we have introduced several scientific problems as examples where combined techniques (e.g., electrophysiology + imaging or molecular biology) are most effective. Thus, encouraging scientists with diverse backgrounds to attempt to utilize patch-clamp electrophysiology. This book was organized by the major patch-clamp application areas, namely pharmacology, physiology, and biophysics. As there are strong overlaps in the techniques utilized in these application areas, we have discussed individual techniques where they are most commonly used. Thus, avoiding any unnec- essary repetition. The first chapter provides examples and step-by-step instructions on how to use whole-cell and single-channel patch-clamp methods for testing drugs in v vi Preface industrial settings. The reader will learn how to perform the electrophysiological method as well as gain insight into the drug-screening process and the standard procedures in using it for this application. A reader will also learn about how electrophysiology can be best utilized in drug research and development. The second part of this chapter provides an opportunity to compare the current automated patch-clamp systems for typical applications and thus filling a gap in this literature. The second chapter provides a wide selection of patch-clamp applica- tions in physiological studies. Emphasis was given to techniques where patch clamp was combined with other methodologies such as photostimu- lation, force measurement, polymerase chain reaction (PCR), cell patterning, or computer modeling. Also, in this chapter, two typical applications of the relatively new dynamic-clamp method are introduced. In addition, emphasis was given to the high diversity of cell types as