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Ion channel research has increased tremendously in the past 35 years since the first publication of the patch clamp technique by Neher and Sakmann in 1976. This is documented by the rising number of publications listed in Pubmed (http://www.ncbi.nlm.nih.gov/pubmed) including the keyword ‘ion channel’ from just 186 hits in 1976 to almost 180,000 hits today. Ion channels attract this great interest due to their pivotal role in the control of fundamental physiological processes in a plethora of different tissues. Moreover, their importance in a wide range of inherited and drug-induced pathologies spanning all major therapeutic areas makes them attractive targets for pharmacological drug screening and potential risk factors when assessing drug safety (Ashcroft, 2006; Clare, 2010; Dunlop 2008; Milligan 2009). Several methods and technologies have been developed to meet the analytical needs for studying ion channels. These approaches have addressed ion channel function directly as well as in the context of the cell and tissue. Scaling of these technologies has allowed ion channel analysis to be carried out on high throughput and high content assay systems. In this Research Topic we want to provide an up-to-date collection of the latest developments and improvements in ion channel screening; defining the cutting edge and indicating further developments required in the future.
Ion channel drug discovery is a rapidly evolving field fuelled by recent, but significant, advances in our understanding of ion channel function combined with enabling technologies such as automated electrophysiology. The resurgent interest in this target class by both pharmaceutical and academic scientists was clearly highlighted by the over-subscribed RSC/BPS 'Ion Channels as Therapeutic Targets' symposium in February 2009. This book builds on the platform created by that meeting, covering themes including advances in screening technology, ion channel structure and modelling and up-to-date case histories of the discovery of modulators of a range of channels, both voltage-gated and non-voltage-gated channels. The editors have built an extensive network of contacts in the field through their first-hand scientific experience, collaborations and conference participation and the organisation of the meeting at Novartis, Horsham, increased the network enabling the editors to draw on the experience of eminent researchers in the field. Interest and investment in ion channel modulation in both industrial and academic settings continues to grow as new therapeutic opportunities are identified and realised for ion channel modulation. This book provides a reference text by covering a combination of recent advances in the field, from technological and medicinal chemistry perspectives, as well as providing an introduction to the new 'ion channel drug discoverer'. The book has contributions from highly respected academic researchers, industrial researchers at the cutting edge of drug discovery and experts in enabling technology. This combination provides a complete picture of the field of interest to a wide range of readers.
Edited by the most prominent person in the field and top researchers at US pharmaceutical companies, this is a unique resource for drug developers and physiologists seeking a molecular-level understanding of ion channel pharmacology. After an introduction to the topic, the authors evaluate the structure and function of ion channels, as well as related drug interaction. A section on assay technologies is followed by a section each on calcium, sodium and potassium channels. Further chapters cover genetic and acquired channelopathies, before the book closes with a look at safety issues in ion channel drug development. For medicinal and pharmaceutical chemists, biochemists, molecular biologists and those working in the pharmaceutical industry.
The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. More than 270 volumes have been published (all of them still in print) and much of the material is relevant even today--truly an essential publication for researchers in all fields of life sciences. Key Features* Expression, purification, and characterization* Activity assays* Kinetic and screening* Design and analysis of substrates and inhibitors* Molecular and structural characterizations.
Ion channels are proteins that make pores in the membranes of excitable cells present both in the brain and the body. These cells are not only responsible for converting chemical and mechanical stimuli into the electrical signals but are also liable for monitoring vital functions. All our activities, from the blinking of our eyes to the beating of our heart and all our senses from smell to sight, touch, taste and hearing are regulated by the ion channels. This book will take us on an expedition describing the role of ion channels in congenital and acquired diseases and the challenges and limitations scientist are facing in the development of drugs targeting these membrane proteins.
Advances in chemistry, biology and genomics coupled with laboratory automation and computational technologies have led to the rapid emergence of the multidisciplinary field of chemical genomics. This edited text, with contributions from experts in the field, discusses the new techniques and applications that help further the study of chemical genomics. The beginning chapters provide an overview of the basic principles of chemical biology and chemical genomics. This is followed by a technical section that describes the sources of small-molecule chemicals; the basics of high-throughput screening technologies; and various bioassays for biochemical-, cellular- and organism-based screens. The final chapters connect the chemical genomics field with personalized medicine and the druggable genome for future discovery of new therapeutics. This book will be valuable to researchers, professionals and graduate students in many fields, including biology, biomedicine and chemistry.
The New Benchmark for Understanding the Latest Developments of Ion ChannelsIon channels control the electrical properties of neurons and cardiac cells, mediate the detection and response to sensory stimuli, and regulate the response to physical stimuli. They can often interact with the cellular environment due to their location at the surface of ce
A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.
Scores of talented and dedicated people serve the forensic science community, performing vitally important work. However, they are often constrained by lack of adequate resources, sound policies, and national support. It is clear that change and advancements, both systematic and scientific, are needed in a number of forensic science disciplines to ensure the reliability of work, establish enforceable standards, and promote best practices with consistent application. Strengthening Forensic Science in the United States: A Path Forward provides a detailed plan for addressing these needs and suggests the creation of a new government entity, the National Institute of Forensic Science, to establish and enforce standards within the forensic science community. The benefits of improving and regulating the forensic science disciplines are clear: assisting law enforcement officials, enhancing homeland security, and reducing the risk of wrongful conviction and exoneration. Strengthening Forensic Science in the United States gives a full account of what is needed to advance the forensic science disciplines, including upgrading of systems and organizational structures, better training, widespread adoption of uniform and enforceable best practices, and mandatory certification and accreditation programs. While this book provides an essential call-to-action for congress and policy makers, it also serves as a vital tool for law enforcement agencies, criminal prosecutors and attorneys, and forensic science educators.
The Model Rules of Professional Conduct provides an up-to-date resource for information on legal ethics. Federal, state and local courts in all jurisdictions look to the Rules for guidance in solving lawyer malpractice cases, disciplinary actions, disqualification issues, sanctions questions and much more. In this volume, black-letter Rules of Professional Conduct are followed by numbered Comments that explain each Rule's purpose and provide suggestions for its practical application. The Rules will help you identify proper conduct in a variety of given situations, review those instances where discretionary action is possible, and define the nature of the relationship between you and your clients, colleagues and the courts.