Modulation of Presynaptic Calcium Channels

ISBN-13: 9789400763333 / Angielski / Twarda / 2013 / 365 str.

Gary Stephens; Sumiko Mochida

Opis

This book brings together leading international experts to discuss recent advances in the regulation of presynaptic voltage-gated Ca2+ channels (VGCCs), key signal transducers that represent one of the most widely modulated proteins in the body. It is now commonly accepted that presence of the VGCC complex defines an excitable cell. At a basic level, VGCCs transduce membrane potential change to chemical neurotransmitter release at presynaptic terminals. However, on-going scientific research, presented here, in areas including neuroscience, electrophysiology, pharmacology, biochemistry and, increasingly, proteomics, has revealed the widespread nature of modulation of the presynaptic VGCC complex. This book reviews and discusses the following topics: * The fundamental role of the VGCC pore-forming CaVa subunit, and some of their binding partners, in presynaptic function and synaptic plasticity. * Modulation of presynaptic CaVa subunits by auxiliary CaVb and a2d subunits and by their major interaction partners, such as active zone scaffolding proteins, synaptic proteins, G proteins and small GTPases, which, together, contribute to the VGCC proteome. * Work at the cutting edge of research, including how direct electrophysiology recordings from presynaptic terminals and introduction of synthetic CaVa peptides into presynaptic terminals has expanded our knowledge of VGCC function. * Evidence emerging over the last decade demonstrating that VGCC subunits represent bona fide molecular targets for therapeutic drug discovery. This development is illustrated by the introduction of the CaV2.2 blocker ziconotide, which represents an important proof-of-concept, but is best exemplified by the emergence of gabapentinoids, which bind the VGCC auxiliary a2d subunit, as first-line treatments for chronic neuropathic pain. Throughout, chapters are accompanied with illustrative Tables and Figure providing a useful and comprehensive summary of the current

Spis treści

Foreword: Gary Stephens

Overview

1. Spatial and temporal regulation of Ca²⁺ channels; Sumiko Mochida

Interaction partners of calcium channels

2. Neuronal functions of auxiliary calcium channel subunits; Gerald Obermair and Bernd Flucher

3. Reciprocal regulation of neuronal calcium channels by synaptic proteins; Norbert Weiss and Gerald Zamponi

4. Molecular architecture of Ca²⁺ channel complexes organized by β subunits in presynaptic active zones; Akito Nakao, Mitsuru Hirano, Yoshinori Takada, Shigeki Kiyonaka and Yasuo Mori

5. Control of Ca_V2 calcium channels and neurosecretion by heterotrimeric G protein coupled receptors; Mark L. Jewell and Kevin P.M. Currie

6. Regulation of Ca_V2 channels by small GTPases; Pierre Charnet, Frédérique Scamps, Matthieu Rousset, Claudine Menard, Michel Bellis and Thierry Cens

7. Protein interaction partners of Ca_v2.3 R-type voltage-gated calcium channels; Maxine Dibué, Etienne E. Tevoufouet, Andreas Krieger, Alexandra Kiel, Dimitar Evdokimov, Thomas Galetin, Serdar Alpdogan, Isha Akhtar, Sabrina Scharf, Renate Clemens, Kayalvizhi Radhakrishnan, Jürgen Hescheler, Toni Schneider, Marcel A. Kamp

8. Voltage-gated calcium channel signaling to the nucleus; Michel Bellis, Thierry Cens, Claudine Menard, Pierre Charnet and Matthieu Rousset

Mechanisms of studying calcium channel effects

9. Presynaptic Ca²⁺ influx and its modulation at auditory calyceal terminals; Holger Taschenberger, Kun-Han Lin and Shuwen Chang

10. Use of synthetic Ca²⁺ channel peptides to study presynaptic function; Giovanna Bucci, Sumiko Mochida and Gary Stephens

Calcium channel therapeutics

11. Impact of a loss-of-function P/Q type Ca²⁺ channel mutation on excitatory synaptic control of cerebellar Purkinje neurons; David Friel

12. Ca_V2.1 (P/Q) voltage activated Ca²⁺ channels and synaptic transmission in genetic and autoimmune diseases; Osvaldo Uchitel

13. Splicing and editing to customize Ca_V channel structures for optimal neural function; Hua Huang, Juejin Wang and Tuck Wah Soong

14. Presynaptic calcium channels as drug targets for pain; Edward Stevens and Peter Fox

15. Sensory pathway modulation by calcium channel a₂d₁ subunit; Chunyi Zhou and Z. David Luo

Index

Blurb

This book brings together leading international experts to discuss recent advances in the regulation of presynaptic voltage-gated Ca²⁺ channels (VGCCs), key signal transducers that represent one of the most widely modulated proteins in the body. It is now commonly accepted that presence of the VGCC complex defines an excitable cell. At a basic level, VGCCs transduce membrane potential change to chemical neurotransmitter release at presynaptic terminals. However, on-going scientific research, presented here, in areas including neuroscience, electrophysiology, pharmacology, biochemistry and, increasingly, proteomics, has revealed the widespread nature of modulation of the presynaptic VGCC complex.

This book reviews and discusses the following topics:

• The fundamental role of the VGCC pore-forming Ca_Va subunit, and some of their binding partners, in presynaptic function and synaptic plasticity.
• Modulation of presynaptic Ca_Va subunits by auxiliary Ca_Vb and a₂d subunits and by their major interaction partners, such as active zone scaffolding proteins, synaptic proteins, G proteins and small GTPases, which, together, contribute to the VGCC proteome.
• Work at the cutting edge of research, including how direct electrophysiology recordings from presynaptic terminals and introduction of synthetic Ca_Va peptides into presynaptic terminals has expanded our knowledge of VGCC function.
• Evidence emerging over the last decade demonstrating that VGCC subunits represent bona fide molecular targets for therapeutic drug discovery. This development is illustrated by the introduction of the Ca_V2.2 blocker ziconotide, which represents an important proof-of-concept, but is best exemplified by the emergence of gabapentinoids, which bind the VGCC auxiliary a₂d subunit, as first-line treatments for chronic neuropathic pain.

Throughout, chapters are accompanied with illustrative Tables and Figure providing a useful and comprehensive summary of the current state-of-play in this area of significant therapeutic interest. Work described here also provides a solid basis for future research in this important area.