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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 Mitochondria 4 Mitochondrial 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 Ca2+ 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 b Subunits in Voltage-Gated Calcium Channel Functions 95 Thierry Cens, Sophie Restituito, Matthieu Rousset and Pierre Charnet Isolation, Characterization and Cloning 95 Association with Ca2+ 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-Proteins 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 a1 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 Distributions of the Ancillary Subunits b, a2-d and g 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: b Subunits, g 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 Gb 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 a1 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 a1C 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 JÜrg 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 b-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 StÄphanie BarrÅre-Lemaire, Matteo E. Mangoni and Joæl 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, RÄgis 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 JÜrg 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 b-Subunits 362 Other Subunits 364 Index 373
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