Potassium Channels as a Target for Clinical Therapeutics


by

Ivan Kocic

DOI: 10.2174/97816080523561120101
eISBN: 978-1-60805-235-6, 2012
ISBN: 978-1-60805-615-6



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Indexed in: Scopus

This e-book presents an overview of the different substances capable of modulating potassium channels in relation to various clinical ...[view complete introduction]

Table of Contents

Foreword

- Pp. i

Ljiljana Gojkovic Bukarica

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Preface

- Pp. ii

Ivan Kocic

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List of Contributors

- Pp. iii

Ivan Kocic

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Potassium Channels and Cardioprotection

- Pp. 3-20 (18)

Ashan Jayasekera and Aleksandar Jovanović

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Potassium Channels Modulators as Antiarrhytmics

- Pp. 21-42 (22)

Dariusz Kozlowski

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Modulators of K<sup>+</sup> Channels in Diabetology

- Pp. 43-60 (18)

Małgorzata Mysliwiec

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Potassium Channels as a Target in Smooth Muscles and Nerves

- Pp. 61-77 (17)

Ivan Kocic

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Molecular Biology and Mutations of K<sup>+</sup> Channels

- Pp. 78-94 (17)

Izabela Rusiecka and Ivan Kocic

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Glossary

- Pp. 95-96 (2)

Ivan Kocic

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Index

- Pp. 97-98 (2)

Ivan Kocic

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Foreword

This e-book presents an overview of the different substances capable of modulating potassium channels in relation to various clinical indications in cardiology, pulmonology, endocrinology and neurology. The possible benefits and side effects of potassium channel modulators is discussed in correlation with biophysical and pharmacological properties of ion channels. Readers will learn how mutation of K+ channels can be conferred by molecular processes such as alternative splicing, RNA editing and posttranslational modifications. Altogether, this e-book will be of use to clinical practitioners, electrophysiologists and pharmacologists interested in the complicated but fascinating science of potassium channels.

It is shown that congenital and acquired changes in the function of potassium channels contribute to the development of various cardiovascular diseases (arrhythmia, sudden cardiac death, cardiac hypertrophy, cardiomyopathy, arterial hypertension, vasospastic angina pectoris etc.). It has particularly highlighted their importance in generating the action potential of cardiac cells. In cardyomiocytes there are several types of ion channels that could compare with picturesque instruments in the orchestra. Each instrument provides a specific tone, and tones produce a melody - the action potential. As in the orchestra, in which it is sufficient that only one instrument is not playing the right tone and the melody breaks down, so the slightest error in cardiac electrogenesis can be fatal. Authors of this book suggest that the knowledge of the structure, function and regulation of potassium channels, which are directly responsible for the duration of repolarization of cardiomyocytes is of great importance for physicians and scientists.

In particular, they described the different channalopathies of potassium channels. Luckily, it is a disease of one gene, and as such is very rare in the general population. However, they provide the opportunity to examine the relationship between structure, function and physiological roles of individual ion channels.

Finally, it should be noted that although potassium channels have important functions in the body, and they are numerous, currently only potassium channel blockers (sulfonil urea derivatives, antiarythmics of group III) have an important place in modern treatment of cardiovascular diseases. Potassium channel openers (nicorandil, pinacidil, diazoxide, etc.), in spite of all efforts over the past three decades, have not found their place in modern cardiovascular therapy. The authors of this book, whose original experimental research in the field of potassium channel is well recognized in the scientific public, tried to give us answer to the question: “What will be the future of the potassium channel modulator as drugs ?”.By reading this book, we can become a member of a family of scientists who is engaged in the potassium channels story.

Ljiljana Gojkovic Bukarica
Professor of Pharmacology
Institute of Pharmacology
Clinical Pharmacology and Toxicology
Medical Faculty in Belgrade
Serbia


Preface

Apart from my deep fascination for potassium channels since early 90-ies, this family of tetrameric membrane proteins deserves great attention and respect due to several obvious reasons and facts: 78 family members (more than half of all existed voltage-gated ion channels and the third largest family of signaling molecules, following G-protein coupled receptors and protein kinases), one of the oldest group of channels from the evolutionary point of view, and numerous crucial physiological functions giving a grandiose potential for therapeutic use.

Treatment of arrhythmias and diabetes type 2 cannot be imagine today without K+ channels modulators.Therefore, there are two chapters in this book dedicated to that clinical disciplines written by experienced and excellent clinicians and scientists Dr. sci. Malgorzata Mysliwiec and Prof. Dariusz Kozlowski, for which I am extremely grateful. One of the most fascinating type of K+ channels are certainly ATP-sensitive K+ channels (KATP ), the only one so tightly connected to cell metabolism and with a so intriguing participation in such a phenomenon as cardiprotection and preconditioning. Here, I want to express my gratitude to Prof. Aleksandar Jovanovic from Dandee University for participating in this chapter dedicated to KATP, who published several cornerstone papers related to the role of KATP in cardioprotection. Also, I greatly appreciate participation of Dr. Ashan Jayasekera in this chapter.

I decided to prepare one chapter including some other important clinical possibilities in other clinical disciplines such as neurology and hypertensiology, to give to the readers a more complete picture of therapeutic potential of K+ channels modulators. And last but not least, in this book one chapter is dedicated to genetic and molecular biology of K+ channels. I asked my coworker Dr. Izabela Rusiecka for help in preparing this chapter. She is a biotechnologist and molecular pharmacologist and I hope we presented the most relevant information in this attractive field.

Finally, my thanks goes to the publisher, Bentham Science, and especially to Sara Moqeet for help and motivation to prepare this book.

Ivan Kocic
Professor of Experimental and Clinical Pharmacology
Medical University of Gdansk, Poland

List of Contributors

Editor(s):
Ivan Kocic
Medical University of Gdansk
Poland




Contributor(s):
Jayasekera Ashan
Oxford Deanery, Department of Urology
Royal Berkshire Hospital
Reading, RG1 5AQ



Jovanovic Aleksandar
Ninewells Hospital and Medical School, University of Dundee
Dundee DD1 9SY



Kocic Ivan
Department of Pharmacology
Medical University of Gdansk
Debowa Str.23
Gdansk, 80-204
Poland


Kozłowski Dariusz
II Department of Cardiology
Medical University of Gdansk
Poland


Mysliwiec Malgorzata
dr. sci. Pediatricien, Department and Clinic of Pediatrics
Hematology, Oncology and Endocrinology, Medical University of Gdansk
Poland


Rusiecka Izabela
Biotechnologist, Department of Pharmacology
Medical University of Gdansk
Debowa 23
Gdansk, 80-204
Poland




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