Voltage-Gated Calcium Channels Book

Preface ................................................................................................ xiv

1. Ca2+ Chemistry Storage and Transport in Biologic Systems:

An Overview .......................................................................................... 1

Tashi G. Kinjo and Paul P.M. Schnetkamp

Why Ca2+ Unique Chemical and Physical Features ............................... 1

Ca2+ Evolution a Rejection from Cytoplasm .......................................... 2

Ca2+ Signaling and Storage the Endoplasmic Recticulum ...................... 2

The Role of Ca2+ within the ER ............................................................ 3

ER Heterogeneity Ca2+ Tunneling Versus

Ca2+ Compartmentalization .............................................................. 3

Ca2+ Signaling and Storage Mihondria ............................................. 4

Mihondrial Ca2+ Uptake Function and Effects ................................. 4

Ca2+ Buffering; Cytosolic and Lumenal ................................................. 5

Channels that Lead to an Increase in Cytosolic Ca2+ .......................................... 5

Intracellular Ca2+ Release Channels ....................................................... 6

Plasma Membrane Ca2+ Channels ......................................................... 7

Cyclic Nucleotide-Gated Channels ........................................................ 7

P2X Receptors ....................................................................................... 7

SOCE and the TRP Gene Family ......................................................... 8

Mechanisms of Store-Operated Ca2+ Entry ........................................... 8

Mechanisms to Lower Cytosolic Ca2+ .......................................................................... 8

PMCA Gene Family .............................................................................. 9

SERCA Gene Family ............................................................................. 9

NCX Gene Family ................................................................................ 9

NCKX Gene Family.............................................................................. 9

2. Monitoring Intracellular Ca2+ in Brain Slices

with Fluorescent Indicators .................................................................. 12

Sean J. Mulligan and Brian A. MacVicar

Ca2+ Sensitive Fluorescent Chemical Indicators ................................... 12

Single-Wavelength Probes ................................................................... 13

Dual-Wavelength Ratiometric Probes ................................................. 15

Ca2+ Binding Affinity .......................................................................... 16

Ca2+ Indicator Form ............................................................................ 18

Dextran Conjugates ............................................................................. 18

AM-Esters ........................................................................................... 20

Quantitative Measurement of [Ca2+]i .................................................. 21

3. A Brief History of Calcium Channel Discovery .................................... 27

Richard W. Tsien and Curtis F. Barrett

The Key Role of Ca2+ Channels in Cellular Signaling .......................... 27

The Winding Road of Calcium Channel Discovery ............................ 30

The Diversity of Native Ca2+ Channel Currents .................................. 36

4. Biochemical Studies of Voltage-Gated Ca2+ Channels .......................... 48

William A. Catterall

Purification and Biochemical Characterization

of Skeletal Muscle Ca2+ Channels .................................................... 48

Biochemical Properties of Other Cav1 Channels .................................. 53

Biochemical Properties of the Cav2 Family of Ca2+ Channels .............. 54

Interactions of Ca2+ Channels with Intracellular Regulatory

Proteins ........................................................................................... 55

5. Molecular Properties of Voltage-Gated Calcium Channels ................... 61

Terrance P. Snutch, Jean Peloquin, Eleanor Mathews

and John E. McRory

Native Voltage-Gated Ca Channels ..................................................... 61

High Voltage-Activated Ca2+ Channels ............................................... 61

Cloned Calcium Channels ................................................................... 66

Low Voltage-Activated (T-Type) Channels ......................................... 77

Auxiliary Ca2+ Channel Subunits ......................................................... 79

6. Role of â Subunits in Voltage-Gated Calcium Channel Functions ....... 95

Thierry Cens, Sophie Restituito, Matthieu Rousset and Pierre Charnet

Isolation, Characterization and Cloning .............................................. 95

Association with Ca Channels ............................................................. 97

Role in Channel Expression and Targeting .......................................... 98

Role in Channel Properties: Activation, Inactivation

and Facilitation ............................................................................... 99

Role in Channel Regulation by Heterotrimeric G-Protein ................. 103

7. Distribution and Targeting Mechanisms of Voltage Activated

Ca2+ Channels .................................................................................... 113

Stefan Herlitze and Melanie D. Mark

Distribution of Ca2+ Channel Types Specified by Their Pore

Forming á1 Subunit ..................................................................... 113

Distribution of L-Type Channels ...................................................... 113

Distribution of P/Q-, N- and R-Type Channels ................................ 116

Cav2 in Pancreas ................................................................................ 121

Distribution of T-Type Channels ...................................................... 121

Distribution of the Ancillary Subunit â, á2-ä and ã .......................... 122

Mechanisms of Ca2+ Channel Targeting: Transport from the ER

to the Plasma Membrane and Specified Subcellular Structures ...... 125

Ca2+ Channel Complex Formation in Heterologous Expression

Systems ......................................................................................... 125

Up and Down Regulation of Ca2+ Channel Expression:

â Subunits, ã Subunits, AKAP and kir/Gem.................................. 127

Targeting of Ca2+ Channels in Skeletal and Cardiac Muscle .............. 128

Sorting of Ca2+ Channels in Polarized Cells: A Correlation

between Polarized Sorting in Epithelial Cells and Neurons ............ 129

8. The Calcium Channel and the Transmitter Release Site .................... 141

Elise F. Stanley and Allen W. Chan

Presynaptic Ca2+ Channel Types ....................................................... 142

Ca2+ Channel Localization at the Presynaptic Nerve Terminal .......... 143

The Calcium Channel and the Triggering of Transmitter Release ..... 144

Calcium Channel Interaction with the Proteins

of the Transmitter Release Site ...................................................... 146

Modulation of Presynaptic Ca2+ Channels ......................................... 148

9. Determinants of G Protein Inhibition of Presynaptic

Calcium Channels .............................................................................. 154

Aparna Nirdosh and Gerald W. Zamponi

Functional Consequences of Direct G Protein Action

on Calcium Channels .................................................................... 155

Stoichiometry between G Proteins and the Calcium Channel ........... 156

G Protein Modulation Depends on the Nature

of the Calcium Channel Subunits .................................................. 157

Gâ Subunits Mediate Calcium Channel Inhibition ........................... 157

Channel and G Protein Structural Basis of G Protein Modulation .... 158

Interactions between G Protein and Protein Kinase C

(PKC) Pathways ............................................................................ 159

RGS Proteins and G Protein Modulation of Calcium Channels ........ 160

Interactions between G Proteins and Synaptic Release Proteins ......... 160

10. Phosphorylation-Dependent Regulation of Voltage-Gated

Ca2+ Channels .................................................................................... 168

Roger A. Bannister, Ulises Meza and Brett A. Adams

Regulation of Ca2+ Channels by Protein Kinase A (PKA) .................. 168

Regulation of Ca2+ Channels by Protein Kinase C (PKC) ................. 171

Regulation of Ca2+ Channels by Protein Kinase G (PKG) ................. 172

Regulation of T-Type Ca2+ Channels by Ca2+/Calmodulin-

Dependent Protein Kinases (CaM Kinases) ................................... 172

Regulation of Ca2+ Channels by Tyrosine Kinases ............................. 173

Regulation of Ca2+ Channels by Mitogen-Activated Protein

(MAP) Kinases .............................................................................. 174

Regulation of Ca2+ Channels by Lipid Kinases .................................. 175

Regulation of Ca2+ Channels by Cyclin-Dependent Kinase

5 (Cdk5) ....................................................................................... 176

Regulation of Ca2+ Channels by Calcineurin ..................................... 176

11. Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels ........... 183

Amy Lee and William A. Catterall

Feedback Regulation of VGCCs by Ca2+ in Paramecium

and Aplysia .................................................................................... 183

Ca2+-Dependent Modulation of Cav1.2 (L-Type) Channels .............. 184

Molecular Determinants of Ca2+-Dependent Modulation

in Cav1.2 Channels ....................................................................... 185

Ca2+-Dependent Regulation of Cav2.1 (P/Q-Type) Channels ........... 187

Differential Modulation of Cav2.1 by CaM and Neuronal

Ca2+-Binding Proteins ................................................................... 190

12. Voltage-Dependent Inactivation of Voltage Gated

Calcium Channels .............................................................................. 194

Mary T. An and Gerald. W. Zamponi

What Have We Learnt from Other Types of Voltage Gated

Cation Channels? .......................................................................... 195

á1 Subunit Structural Inactivation Determinants in High

Voltage Activated Channels ........................................................... 197

Role of Ancillary Subunits in Calcium Channel Inactivation ............. 199

Possible Molecular Mechanism of Calcium Channel Inactivation ..... 200

13. Selective Permeability of Voltage-Gated Calcium Channels ............... 205

William A. Sather

Selectivity by Ion Binding Affinity .................................................... 206

A Multi-Ion Pore Confers High Flux ................................................ 206

Amino Acid Residues of the Selectivity Filter .................................... 208

A Single High-Affinity Locus ............................................................ 211

Non-Equivalence of EEEE Locus Glutamates ................................... 212

Functional Groups That Bind Ca2+ ......................................................................... 213

Structure-Based Selectivity Models .................................................... 215

14. The Run-Down Phenomenon of Ca2+ Channels ................................ 219

Klaus JF Kepplinger and Christoph Romanin

Which Native Calcium Channel Types Exhibit Run-Down? ............. 219

Prevention and Reversal of Channel Run-Down ............................... 220

The Nucleotides ATP and ADP ........................................................ 220

Regulation by Phosphorylation/Dephosphorylation ......................... 222

Is Calpastatin the Regulatory Protein in the Cytoplasm? ................... 222

Molecular Determinants of Calpastatin in the Regulation

of Calcium Channel Activity ......................................................... 223

Which Subunits of the L-Type Calcium Channel Are Involved

in the Run-Down Process? ............................................................ 223

Molecular Determinants for Run-Down in the á1C Subunit ............ 223

Summary of the Molecular Mechanisms and Determinants

of Run-Down ................................................................................ 226

15. Calcium Channels As Therapeutic Targets......................................... 231

Francesco Belardetti and Sian Spacey

L-Type Channels ............................................................................... 231

N-Type Channels .............................................................................. 233

P/Q-Type Channels .......................................................................... 233

T-Type Channels .............................................................................. 235

16. Calcium Channelopathies .................................................................. 240

Nancy M. Lorenzon and Kurt G. Beam

Calcium Channelopathies of the Nervous System ............................. 240

Calcium Channelopathies of Muscle ................................................. 250

17. The Molecular Basis of Ca2+ Antagonist Drug

Action-Recent Developments ............................................................. 262

Jörg Striessnig, Jean-Charles Hoda, Edwin Wappl

and Alexandra Koschak

A Multisubsite Model of the Ca2+ Antagonist Drug

Binding Domains .......................................................................... 264

Towards a Three-Dimensional Model of the DHP

Binding Domain ........................................................................... 266

PAA and BTZ Binding Residues ....................................................... 275

Differences in DHP Sensitivity between Cav1.2 , Cav1.3

and Cav1.4 L-Type Ca2+ Channels ................................................ 275

18. Calcium Channel Block and Inactivation:

Insights from Structure-Activity Studies ............................................. 281

Steffen Hering, Stanislav Sokolov, Stanislav Berjukow,

Rainer Marksteiner, Eva Margreiter and Evgeni N. Timin

Amino Acid Residues Located in the Putative Drug-Binding

Region Affect Drug-Sensitivity and Channel Inactivation ............. 284

Drug-Sensitivity Is Affected by Inactivation Determinants

Located Outside the Putative Drug-Binding Region ..................... 286

â-Subunits Modulate Inactivation and Channel Inhibition ............... 287

Inactivation Determinants and DHP Sensitivity ................................ 287

On the Role of Ca2+-Dependent Inactivation in Drug Sensitivity ...... 290

Simulation of the Drug-Channel Interaction ..................................... 290

19. Block of Voltage-Gated Calcium Channels by Peptide Toxins ........... 294

Christina I. Schroeder, Richard J. Lewis and David J. Adams

L-Type VSCC Antagonists ................................................................ 295

N-Type VSCC Antagonists ............................................................... 300

P/Q-Type VSCC Antagonists ........................................................... 302

R-Type VSCCC Antagonists ............................................................. 303

T-Type Antagonists ........................................................................... 304

20. Calcium Channels in the Heart .......................................................... 309

Stéphanie Barrère-Lemaire, Matteo E. Mangoni and Joël Nargeot

I-Cardiac Ca2+ Channels in Working Myocardial Cells ..................... 309

Cardiac Ca2+ Channels and Pacemaker Activity ................................. 315

21. Post-Genomic Insights into T-Type Calcium Channels

Functions in Neurons ......................................................................... 326

Emmanuel Bourinet, Philippe Lory, Jean Chemin, Steve Dubel,

Régis Lambert, Olivier Poirot, Arnaud Monteil, Anne Feltz

and Joel Nargeot

Contributions of Recombinant Channel Studies ............................... 327

T-Type Channels and Neurophysiology ............................................ 329

22. Voltage-Gated Ca2+ Channels of the Vertebrate Retina:

From the Genetics of Blindness to Encoding the Visual World .......... 334

Melanie E.M. Kelly and Steven Barnes

Ca2+ Channels in the Graded Potential Neurons of the Outer Retina . 336

Ca2+ Channel Subtypes in Spiking Cells of the Inner Retina ............. 338

Differential Expression of Ca2+ Channel Subtypes during Retinal

Development ................................................................................. 341

23. Exploring the Function and Pharmacotherapeutic of Potential

Voltage-Gated Ca2+ Channels with Gene-Knockout Models .............. 346

Jörg Striessnig and Alexandra Koschak

The Cav1 (L-Type) Ca2+ Channel Family .......................................... 348

The Cav2 (P/Q-, N- and R-Type) Ca2+ Channel Family ................... 353

The Cav3 (T-Type) Ca2+ Channel Family ......................................... 359

Ca2+ Channel â-Subunits .................................................................. 362

Other Subunits .................................................................................. 364

Index .................................................................................................. 373