Physiology and Pathology of Chloride Transporters and Channels in the Nervous System: From Molecules to Diseases

The importance of chloride ions in cell physiology has not been fully recognized until recently, in spite of the fact that chloride (Cl-), together with bicarbonate, is the most abundant free anion in animal cells, and performs or determines fundamental biological functions in all tissues. For many years it was thought that Cl- was distributed in thermodynamic equilibrium across the plasma membrane of most cells. Research carried out during the last couple of decades has led to a dramatic change in this simplistic view. We now know that most animal cells, neurons included, exhibit a non-equilibrium distribution of Cl- across their plasma membranes. Over the last 10 to 15 years, with the growth of molecular biology and the advent of new optical methods, an enormous amount of exciting new information has become available on the molecular structure and function of Cl- channels and carriers. In nerve cells, Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control. Disruption of Cl- homeostasis in neurons underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation. This book is about how chloride ions are regulated and how they cross the plasma membrane of neurons. It spans from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases.

The first comprehensive book on the structure, molecular biology, cell physiology, and role in diseases of chloride transporters / channels in the nervous system in almost 20 yearsChloride is the most abundant free anion in animal cells. THis book summarizes and integrates for the first time the important research of the past two decades that has shown that Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume controlThe first book that systematically discusses the result of disruption of Cl- homeostasis in neurons which underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammationSpanning topics from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseasesInvolves all of the leading researchers in the fieldIncludes an extensive introductory section that covers basic thermodynamic and kinetics aspects of Cl- transport, as well as current methods for studying Cl- regulation, spanning from fluorescent dyes in single cells to knock-out models to make the book available for a growing population of graduate students and postdocs entering the field

Section I Overview of chloride transporters and channels

1. Chloride Channels: An Historical Perspective by H. Criss Hartzell

2. Sodium-Coupled Chloride Cotransporters: Discovery and Newly Emerging Concepts by John Russell

3. Pathophysiology of the K+-Cl- Cotransporters: Paths to Discovery and Overview by John S. Gibson, J. Clive Ellory, Norma C. Adragna and Peter K. Lauf

4. From Cloning to Structure, Function, and Regulation of Chloride-dependent and Independent Bicarbonate Transporters by Michael F. Romero, Min-Hwang Chang and David Mount

5. Thermodynamics and Kinetics of chloride transport in Neurons: An Outline by F. Javier Alvarez-Leefmans and Eric Delpire

Section II Current methods for studying chloride regulation

6. Chemical and GFP-based Fluorescent Chloride Indicators by Alan S. Verkman

7. Clomeleon, a Genetically-encoded Chloride Indicator by Ken Berglund, Thomas Kuner and George J. Augustine

8. Gramicidin Perforated Patch by Norio Akaike

9. Measuring Electroneutral Chloride-dependent Ion Fluxes in Heterologous Expression Systems by Kenneth

Gagnon

10. Knockout models of cation chloride cotransporters by Nicole Garbarini and Eric Delpire

Section III From cloning to structure, function and regulation of chloride channels

11. The NKCC and NCC genes: An in silico view by Mauricio Di Fulvio and F. Javier Alvarez-Leefmans

12. The ClC Family of Chloride Channels and Transporters by Tobias Stauber, Gaia Novarino and Thomas J. Jentsch

13. Calcium-Activated Chloride Channels by Fiona Britton, Normand Leblanc and James L. Kenyon

14. GABAA Receptor Channels by Robert L. Macdonald and Emmanuel J. Botzolakis

15. The Puzzles of Volume-Activated Anion Channels by Yasunobu Okada, Kaori Sato, Abduqodir H. Toychiev, Makoto Suzuki, Amal K. Dutta, Hana Inoue and Ravshan Z. Sabirov

16. The Sodium-Dependent Chloride Cotransporters by Gerardo Gamba

17. The Potassium-Chloride Cotransporters: from Cloning to Structure and Function by John A. Payne

18. Regulation of Cation-Chloride Cotransporters by Gerardo Gamba, Nicole Garbarini and Eric Delpire

Section IV Cation-chloride cotransporters in neural function and dysfunction

19. GABA, Glycine and Cation-Chloride Cotransporterts in Retinal Function and Development by Noga Vardi and ling-Li Zhang

20. Chloride-based Signal Amplification in Olfactory Sensory Neurons by Stephan Frings

21. Cochlear and Vestibular Function and Dysfunction by Daniel C. Marcus and Philine Wangemann

22. Presynaptic inhibition, pain and neurogenic inflammation by F. Javier Alvarez-Leefmans

23. Modulation of Chloride Homeostasis by Microglia by Yves De Koninck

24. Cation-Chloride Cotransporters as Pharmacological Targets in the Treatment of Epilepsy by Kristopher T. Kahle and Kevin Staley

25. The Role of Cation-Chloride Cotransporters in Brain Ischemia by Dandan Sun, Doug Kintner and Brooks B. Pond

26. Chloride Transport in Glioma Growth and Cell Invasion by Harald Sontheimer

27. The Sodium-Potassium-Chloride Cotransporter, Human Cytomegalovirus, and the Cell Cycle by John M. Russell

Section V Cation-chloride cotransport in Choroid Plexus and blood brain barrier

28. Chloride Transporters as Water Pumps: Elements in a New Model of Epithelial Water Transport by Nanna MacAulay, Steffen Hamann, and Thomas Zeuthen

29. Choroid plexus and chloride transport by Peter D. Brown , Sarah L. Davies and Ian D. Millar

30. Ion and Water Transport Across the Blood-Brain Barrier by Martha E. O’Donnell