TRP ion channels were first described in Drosophila melanogaster in 1989 and in mammals several years later. In 1997, TRPV1, a member of the TRP channel superfamily (now with more than 60 members in vertebrates and invertebrates but not in bacteria and plants), was described to respond to the pungent ingredients of hot pepper, then named capsaicin receptor. Ever since we have witnessed an explosion of activity in this field of scientific inquiry for obvious reasons. TRP ion channels are critical elements in signal transduction of cellular signaling cascades and of neurosensory processes, which are involved in all five senses.

This book, TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades presents 31 chapters written by researchers who have made these key discoveries, such as Dr. Lutz Birnbaumer who discovered mammalian TRP channels, and who continues to conduct TRP ion channel research at the cutting edge of this hyperdynamic area. Because of the burgeoning nature of the field, this book does not represent an all-comprehensive view on TRP channel biology. However, it does shed light on selected topics of outstanding interest in the TRP arena, such as signal transduction in axonal pathfinding, and vascular, renal, auditory, and nociceptive functioning, to name a few, and the spotlight is cast by an international cast of outstanding chapter authors.

Contents

• Series Preface
• Preface
• The Editors
• Contributors
• 1. The TRPC Family of Ion Channels: Relation to the TRP Superfamily and Role in Receptor- and Store-Operated Calcium Entry
  Joel Abramowitz, Eda Yildirim, and Lutz Birnbaumer.
  • TRP CHANNELS: DIVERSITY OF FORM AND FUNCTION
  • TRP SUPERFAMILY GENES AND THEIR GENE PRODUCTS
  • MECHANISM(S) OF TRPC ACTIVATION
  • STUDIES ON THE ROLE(S) OF TYROSINE PHOSPHORYLATION IN TRPC FUNCTION
  • REFERENCES
• 2. Multiple Mechanisms of TRPC Activation
  James W. Putney Jr.
  • INTRODUCTION
  • TRPCS: MECHANISMS OF REGULATION IN TRANSFECTO
  • MECHANISMS OF TRPC ACTIVATION IN SITU
  • SUMMARY
  • REFERENCES
• 3. TRPC2 and the Molecular Biology of Pheromone Detection in Mammals
  Emily R. Liman and Catherine Dulac.
  • INTRODUCTION
  • THE MOLECULAR BIOLOGY OF PHEROMONE SENSING IN MAMMALS
  • TRPC2 PROTEIN STRUCTURE AND BINDING PARTNERS
  • CONCLUSION
  • REFERENCES
• 4. TRP Channels and Axon Pathfinding
  Kai Cui and Xiao-bing Yuan.
  • OVERVIEW OF NERVE PATHFINDING
  • CALCIUM SIGNAL IN GROWTH CONE TURNING
  • TRPCS’ FUNCTION IN NERVE GUIDANCE
  • POSSIBLE ROLES OF TRP CHANNELS IN NEURONAL MIGRATION
  • CONCLUSION
  • REFERENCES
• 5. TRPV1 Receptors and Signal Transduction
  Tamara Rosenbaum and Sidney A. Simon.
  • INTRODUCTION
  • TRPV1 ACTIVATORS
  • MODULATION OF TRPV1 ACTIVITY BY CELLULAR COMPONENTS
  • REFERENCES
• 6. Complex Regulation of TRPV1 by Vanilloids
  Arpad Szallasi and Peter M. Blumberg.
  • INTRODUCTION
  • THE VANILLOID RECEPTOR TRPV1 AND ITS ENDOGENOUS LIGANDS, THE “ENDOVANILLOIDS”
  • TRPV1 IN THE RESTING STATE
  • MOLECULAR ACTIVATORS OF TRPV1
  • REGULATION BY NGF OF TRPV1 MAY PLAY A CENTRAL ROLE IN INFLAMMATORY HYPERALGESIA
  • MODULATION OF TRPV1 BY PROTEIN KINASES
  • SHUFFLING OF TRPV1 AMONG VARIOUS SUBCELLULAR COMPARTMENTS
  • REGULATION OF TRPV1 BY MAST CELLS
  • HOW CAN A SINGLE RECEPTOR MEDIATE RESPONSES WITH DISSIMILAR STRUCTURE-ACTIVITY RELATIONS?
  • DIVERSITY OF BEHAVIOR OF EXOGENOUS LIGANDS
  • TISSUE AND CELLULAR EXPRESSION OF VR1 AND ITS SPLICE VARIANTS
  • POSSIBLE REGULATION OF TRPV1 BY SPLICE VARIANTS
  • REGULATION OF TRPV1 BY SERUM STEROIDS
  • REGULATION OF TRPV1 BY (NEURO)ENDOCRINE FACTORS
  • TRPV1 MAY SUBSERVE OPPOSING ACTIONS AT THE WHOLE ANIMAL LEVEL
  • TRPV1 IS COEXPRESSED WITH ITS RELATIVES ON SENSORY NEURONS WITH OVERLAPPING ACTIVITY
  • PHARMACOLOGICAL OVERLAP BETWEEN TRPV1 AND ITS RELATIVES
  • TRPV1 EXPRESSION MAY CHANGE UNDER PATHOLOGICAL CONDITIONS
  • CONCLUDING REMARKS
  • REFERENCES
• 7. TRPV2: A Calcium-Permeable Cation Channel Regulated by Insulin-Like Growth Factors
  Itaru Kojima and Masahiro Nagasawa.
  • REQUIREMENT OF CALCIUM ENTRY FOR CELL-CYCLE PROGRESSION
  • PROPERTY OF THE IGF-REGULATED CHANNEL
  • MOLECULAR IDENTIFICATION OF THE IGF-REGULATED CHANNEL
  • REGULATION OF TRPV2 BY IGF-I
  • REGULATION OF TRANSLOCATION OF TRPV2
  • REFERENCES
• 8. Molecular Mechanisms of TRPV4 Gating
  Stefan Heller and Roger G. O’Neil.
  • INTRODUCTION
  • TRPV4 STRUCTURE
  • EMERGING MECHANISM OF CHANNEL ACTIVATION
  • MOLECULAR INSIGHTS INTO CHANNEL SELECTIVITY AND GATING
  • SUMMARY
  • REFERENCES
• 9. TRPV4: A Multifunctional Nonselective Cation Channel with Complex Regulation
  Tim D. Plant and Rainer Strotmann.
  • INTRODUCTION
  • TISSUE EXPRESSION OF TRPV4
  • REGULATION OF TRPV4 ACTIVITY
  • PROPERTIES OF CHANNELS FORMED BY TRPV4
  • CONCLUSIONS
  • REFERENCES
• 10. TRPV4 and TRPM3 as Volume-Regulated Cation Channels
  Christian Harteneck and Günter Schultz.
  • INTRODUCTION
  • TRPV4
  • TRPM3
  • SUMMARY
  • REFERENCES
• 11. TRPA1 : A Sensory Channel of Many Talents
  Marilia Z. P. Guimaraes and Sven-Eric Jordt.
  • INTRODUCTION
  • TRPA1 IN THE SENSORY NEURAL RESPONSE TO MUSTARD OIL
  • ACTIVATION OF TRPA1 BY CANNABINOIDS
  • TRPA1 IN COLD SENSATION: QUESTIONS AND ANSWERS
  • TRPA1 IS A RECEPTOR-OPERATED CHANNEL ACTING IN CONCERT WITH TRPV1
  • TRPA1 AS A MULTIPLE IRRITANT SENSOR
  • CONCLUSION
  • REFERENCES
• 12. TRPA1 in Auditory and Nociceptive Organs
  Jaime García-Añoveros and Anne Duggan.
  • DISTRIBUTION OF TRPA1 IN THE INNER EAR
  • FUNCTIONAL TESTS OF TRPA1 IN THE INNER EAR
  • COMPARING CHANNEL PROPERTIES OF TRPA1 AND OF THE HAIR CELL TRANSDUCER
  • DISTRIBUTION OF TRPA1 IN SENSORY GANGLIA
  • THE FUNCTION OF TRPA1 IN NOCICEPTORS
  • A CHANNEL PROPERTY OF TRPA1 FOR NOCICEPTION
  • TRPA1 IN INVERTEBRATES
  • NOTE
  • REFERENCES
• 13. TRPM8: The Cold and Menthol Receptor
  David D. McKemy.
  • INTRODUCTION
  • COLD SENSING AND MENTHOL
  • THE HUNT FOR A MENTHOL RECEPTOR
  • THE CLONING OF A COLD AND MENTHOL RECEPTOR
  • TRPM8 HAS PROPERTIES SIMILAR TO THOSE OF COLD RECEPTORS
  • OTHER COOLING COMPOUNDS ACTIVATE TRPM8
  • REGULATION OF TRPM8 CURRENTS
  • MECHANISM OF COLD ACTIVATION
  • A ROLE FOR TRPM8 OUTSIDE THE NERVOUS SYSTEM
  • CONCLUSIONS
  • REFERENCES
• 14. Activation Mechanisms and Functional Roles of TRPP2 Cation Channels
  Aurélie Giamarchi and Patrick Delmas.
  • INTRODUCING THE TRPP PROTEIN SUBFAMILY
  • MUTATIONS IN TRPP2 AND POLYCYSTIN-1 CAUSE ADPKD
  • LOCALIZATION AND TRAFFICKING OF TRPP2
  • TRPP2: A CA²⁺-REGULATED CATION CHANNEL LOCATED IN THE ENDOPLASMIC RETICULUM
  • COASSEMBLY OF PKD1 AND TRPP2 RECONSTITUTES A CELL SURFACE CA²⁺-PERMEABLE CATION CHANNEL WITH MULTIPLE FUNCTIONS
  • ACTIVATION OF THE PKD1–TRPP2 COMPLEX
  • TRPP2: A BONA FIDE MECHANOSENSITIVE CHANNEL?
  • CONCLUDING REMARKS
  • REFERENCES
• 15. The Ca²⁺-Activated TRP Channels: TRPM4 and TRPM5
  Emily R. Liman.
  • CLONING, DISTRIBUTION, AND STRUCTURE OF TRPM4 AND TRPM5
  • ION PERMEABILITY, UNITARY PROPERTIES, AND SPECIFIC BLOCKERS OF TRPM4 AND TRPM5
  • SENSITIVITY OF TRPM4 AND TRPM5 TO INTRACELLULAR CA²⁺
  • ACTIVATION OF TRPM4 AND TRPM5 BY VOLTAGE
  • REGULATION OF TRPM4 AND TRPM5 BY PIP₂
  • FUNCTION OF TRPM4 AND TRPM5
  • REFERENCES
• 16. Genetics Can Be Painless: Molecular Genetic Analysis of Nociception in Drosophila
  W. Daniel Tracey Jr.
  • A DROSOPHILA MODEL FOR NOCICEPTION
  • MUTATIONS IN A TRPA ION CHANNEL INCREASE MECHANICAL AND THERMAL NOCICEPTION THRESHOLDS
  • DISTINCT CELLULAR AND MOLECULAR PATHWAYS FOR INNOCUOUS AND NOXIOUS TOUCH DETECTION IN DROSOPHILA
  • THERMO TRP CHANNELS ARE TEMPERATURE SENSORS IN MAMMALS
  • MULTIPLE TRPA CHANNELS ARE HEAT ACTIVATED IN FLIES
  • EVIDENCE FOR COMBINATORIAL ENCODING OF TEMPERATURE RESPONSE
  • PUTATIVE FUNCTIONS FOR THE HIGH-THRESHOLD AND LOW-THRESHOLD TYPES OF THERMOSENSORY NEURONS
  • THE MAMMALIAN TRPA1 CHANNEL IS ACTIVATED BY IRRITANTS THAT ELICIT SENSATIONS OF BURNING PAIN
  • TRP CHANNELS HAVE BEEN IMPLICATED IN MECHANOTRANSDUCTION
  • REFERENCES
• 17. TRPV Family Ion Channels and Other Molecular Components Required for Hearing and Proprioception in Drosophila
  Changsoo Kim.
  • INTRODUCTION
  • THE DROSOPHILA CHORDOTONAL ORGANS
  • DROSOPHILA TRPV CHANNELS: NANCHUNG AND INACTIVE
  • CONCLUDING REMARKS
  • REFERENCES
• 18. The TRPV Channel in C. elegans Serotonergic Neurons
  Ji Ying Sze.
  • INTRODUCTION
  • CONSERVATION OF THE SEROTONERGIC SYSTEM IN C. ELEGANS
  • THE FUNCTION AND MECHANISM OF OCR-2 AND OSM-9 IN SEROTONERGIC NEURONS
  • SPECIFICITY OF OCR-2 AND OSM-9 SIGNALING PATHWAYS IN DIFFERENT SENSORY NEURONS
  • TRP CHANNELS IN MAMMALIAN SEROTONERGIC SYSTEMS?
  • REFERENCES
• 19. TRP Channel Functioning in Mating and Fertilization
  X. Z. Shawn Xu and Maureen M. Barr.
  • TRPP
  • THE TRPC CHANNEL SUBFAMILY IN C. ELEGANS
  • REFERENCES
• 20. The Role of TRP Channels in Thermosensation
  Makoto Tominaga.
  • INTRODUCTION
  • HEAT RECEPTORS
  • WARM RECEPTORS
  • COLD RECEPTORS
  • THERMAL NOCICEPTION THROUGH TRP CHANNELS IN INVERTEBRATES
  • CONCLUSION
  • REFERENCES
• 21. Voltage and Temperature Gating of ThermoTRP Channels
  Ramon Latorre, Guillermo Vargas, and Gerardo Orta; Sebastian Brauchi.
  • INTRODUCTION
  • THERMOTRP BIOPHYSICS
  • PROTEIN DENATURATION, LIPIDS, AND THERMOTRP CHANNELS
  • MULTISTATE NATURE OF THERMOTRPS’ OPENING PROCESS
  • A MINIMUM MODEL THAT EXPLAINS THE CHANGE IN LENGTH OF BURSTS AND GAPS WITH TEMPERATURE
  • AN ALLOSTERIC MODEL FOR THERMOTRP ACTIVATION
  • REFERENCES
• 22. TRPV Channels’ Function in Osmo- and Mechanotransduction
  Wolfgang B. Liedtke.
  • INTRODUCTION: THE TRPV SUBFAMILY
  • HETEROLOGOUS CELLULAR EXPRESSION SYSTEMS
  • OSMO- AND MECHANOTRP TRPV1: ANIMAL FINDINGS
  • OSMO- AND MECHANOTRP TRPV2: TISSUE CULTURE DATA
  • OSMO- AND MECHANOTRP TRPV4: TISSUE CULTURE AND ANIMAL DATA
  • C. ELEGANS TRPV CHANNELS AND MECHANO-, OSMOSENSATION
  • OUTLOOK FOR FUTURE RESEARCH ON TRP CHANNELS
  • REFERENCES
• 23. TRP Channel Trafficking
  Rosa Planells-Cases and Antonio Ferrer-Montiel.
  • TRP DEFINITIONS AND FAMILIES
  • TRP TRANSLOCATION AS AN ACTIVATION AND REGULATORY MECHANISM
  • CONCLUDING REMARKS
  • REFERENCES
• 24. Protein–Protein Interactions in TRPC Channel Complexes
  Petra Eder, Rainer Schindl, Christoph Romanin, and Klaus Groschner.
  • INTRODUCTION
  • SUBUNIT ASSEMBLY AND ANCHORING OF TRPC CHANNELS WITHIN MULTIMOLECULAR SIGNALPLEXES
  • CELLULAR TRAFFICKING OF TRPC CHANNEL COMPLEXES
  • TRPC CHANNEL GATING
  • TRPC SIGNALING PARTNERSHIPS
  • CONCLUDING REMARKS AND PERSPECTIVES
  • REFERENCES
• 25. Structural Insights into the Function of TRP Channels
  Rachelle Gaudet.
  • STRUCTURAL SCAFFOLD OF TRP CHANNELS
  • THE TRANSMEMBRANE REGION
  • CYTOSOLIC DOMAINS
  • OLIGOMERIZATION OF CYTOSOLIC DOMAINS
  • SUMMARY
  • REFERENCES
• 26. Functional Significance of Transient Receptor Potential Channels in Vascular Function
  Scott Earley, Stacey Reading, and Joseph E. Brayden.
  • INTRODUCTION
  • TRP CHANNEL FUNCTION IN VASCULAR SMOOTH MUSCLE CELLS
  • TRP CHANNEL FUNCTION IN VASCULAR ENDOTHELIAL CELLS
  • SUMMARY AND FUTURE PERSPECTIVES
  • REFERENCES
• 27. Role of TRPV4 in the Mechanotransduction of Shear Stress in Endothelial Cells
  Ralf Köhler and Joachim Hoyer.
  • CA²⁺ AND ENDOTHELIAL FUNCTION
  • TRPS IN THE ENDOTHELIUM
  • TRPV4 IN THE ENDOTHELIUM
  • TRPV4 AND ENDOTHELIUM-DEPENDENT VASODILATATION
  • TRPV4-MEDIATED VASODILATATION IS NITRIC OXIDE DEPENDENT IN CAROTID ARTERIES
  • A FUNCTIONAL ROLE OF TRPV4 IN ENDOTHELIAL MECHANOTRANSDUCTION?
  • ENDOTHELIAL TRP CHANNELS AND CARDIOVASCULAR DISEASE
  • DO ENDOTHELIAL CA²⁺-PERMEABLE CATION CHANNELS LIKE TRPV4 REPRESENT NOVEL PHARMACOTHERAPEUTIC TARGETS FOR ANTI-HYPERTENSIVE THERAPY?
  • REFERENCES
• 28. A New Insight into the Function of TRPV2 in Circulatory Organs
  Katsuhiko Muraki, Munekazu Shigekawa, and Yuji Imaizumi.
  • INTRODUCTION
  • CONCLUSIONS
  • REFERENCES
• 29. The Role of TRPV4 in the Kidney
  David M. Cohen.
  • ACTIVATION OF TRPV4
  • TRPV4 IN CELLULAR OSMOREGULATION
  • TRPV4 IN SYSTEMIC OSMOREGULATION
  • SUMMARY
  • REFERENCES
• 30. The TRPV4 Channel in Ciliated Epithelia
  Yaniré N. Andrade, Jacqueline Fernandes, Ivan M. Lorenzo, Maite Arniges, and Miguel A. Valverde.
  • CELL CALCIUM SIGNALING IN EPITHELIA
  • TRP CHANNELS IN EPITHELIA
  • THE CILIATED EPITHELIUM
  • TRPV4 AND CELL VOLUME REGULATION IN CILIATED EPITHELIA
  • TRPV4 AND REGULATION OF CILIARY BEAT FREQUENCY
  • CONCLUSIONS
  • REFERENCES
• 31. Protease-Activated Receptors: Mechanisms by Which Proteases Sensitize TRPV Channels to Induce Neurogenic Inflammation and Pain
  Andrew Grant, Silvia Amadesi, and Nigel W. Bunnett.
  • INTRODUCTION
  • PAR CLEAVAGE AND ACTIVATION
  • MECHANISMS OF PAR SIGNAL TRANSDUCTION
  • PARs AND PROTEASE SIGNALING IN THE NERVOUS SYSTEM
  • CONCLUSIONS AND FUTURE PERSPECTIVES
  • REFERENCES

Series editors: Sidney A Simon and Miguel AL Nicolelis

This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use.