Written by the world's leading experts
A highly important scientific field
Clear relevance to current therapeutic drug development
This book will bring together leading international experts to discuss recent advances in basic scientific knowledge regarding the regulation of presynaptic Ca2+ channels. Importantly, Ca2+ channels represent one of the most widely modulated proteins in the body, being the target of a range of effector pathways and drugs; this range will be fully represented here. A number of therapeutic drugs target the Ca2+ channel complex, including the anti-epileptic gabapentinoid and analgesic ziconotide drugs and the pharmaceutical industry is searching for Ca2+ channel blocking drugs, particularly in the pain, epilepsy, ataxia and migraine areas. Such potential future therapies will be discussed here. Scientific disciplines will focus on electrophysiological studies, but will extend to neuroscience, genetics and biochemical areas. The work described will represent advances at the cutting edge of current neuroscience research and is timely and highly appropriate for the Springer book series.
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 ? subunits in presynaptic active zones; Akito Nakao, Mitsuru Hirano, Yoshinori Takada, Shigeki Kiyonaka and Yasuo Mori
5. Control of CaV2 calcium channels and neurosecretion by heterotrimeric G protein coupled receptors; Mark L. Jewell and Kevin P.M. Currie
6. Regulation of CaV2 channels by small GTPases; Pierre Charnet, Frédérique Scamps, Matthieu Rousset, Claudine Menard, Michel Bellis and Thierry Cens
7. Protein interaction partners of Cav2.3 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 effects9. 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. CaV2.1 (P/Q) voltage activated Ca2+ channels and synaptic transmission in genetic and autoimmune diseases; Osvaldo Uchitel
13. Splicing and editing to customize CaV 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
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 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.
This book presents recent advances in knowledge of the regulation of presynaptic Ca2+ channels. These represent one of the most widely modulated proteins in the body, target of a range of effector pathways and drugs; this range will be fully represented here.
Spatial and temporal regulation of Ca2+ channels.- Neuronal functions of auxiliary calcium channel subunits.- Reciprocal regulation of neuronal calcium channels by synaptic proteins.- Molecular architecture of Ca2+ channel complexes organized by beta subunits in presynaptic active zones.- Control of CaV2 calcium channels and neurosecretion by heterotrimeric G protein coupled receptors.- Regulation of CaV2 channels by small GTPases.- Protein interaction partners of Cav2.3 R-type voltage-gated calcium channels.- Voltage-gated calcium channel signaling to the nucleus.- Presynaptic Ca2+ influx and its modulation at auditory calyceal terminals.- Use of synthetic Ca2+ channel peptides to study presynaptic function.- Impact of a loss-of-function P/Q type Ca2+ channel mutation on excitatory synaptic control of cerebellar Purkinje neurons.- CaV2.1 (P/Q) voltage activated Ca2+ channels and synaptic transmission in genetic and autoimmune diseases.- Splicing and editing to customize CaV channel structures for optimal neural function.- Presynaptic calcium channels as drug targets for pain.- Sensory pathway modulation by calcium channel a2d1 subunit.
Inhaltsverzeichnis
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 ß subunits in presynaptic active zones; Akito Nakao, Mitsuru Hirano, Yoshinori Takada, Shigeki Kiyonaka and Yasuo Mori
5. Control of CaV2 calcium channels and neurosecretion by heterotrimeric G protein coupled receptors; Mark L. Jewell and Kevin P.M. Currie
6. Regulation of CaV2 channels by small GTPases; Pierre Charnet, Frédérique Scamps, Matthieu Rousset, Claudine Menard, Michel Bellis and Thierry Cens
7. Protein interaction partners of Cav2.3 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. CaV2.1 (P/Q) voltage activated Ca2+ channels and synaptic transmission in genetic and autoimmune diseases; Osvaldo Uchitel
13. Splicing and editing to customize CaV 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
Klappentext
This book will bring together leading international experts to discuss recent advances in basic scientific knowledge regarding the regulation of presynaptic Ca2+ channels. Importantly, Ca2+ channels represent one of the most widely modulated proteins in the body, being the target of a range of effector pathways and drugs; this range will be fully represented here. A number of therapeutic drugs target the Ca2+ channel complex, including the anti-epileptic gabapentinoid and analgesic ziconotide drugs and the pharmaceutical industry is searching for Ca2+ channel blocking drugs, particularly in the pain, epilepsy, ataxia and migraine areas. Such potential future therapies will be discussed here. Scientific disciplines will focus on electrophysiological studies, but will extend to neuroscience, genetics and biochemical areas. The work described will represent advances at the cutting edge of current neuroscience research and is timely and highly appropriate for the Springer book series.
Written by the world's leading experts
A highly important scientific field
Clear relevance to current therapeutic drug development
