ABSTRACT

Cation channels encoded by the gene superfamily of transient receptor potentials (TRPs) are characterized by a wide variety of activation triggers that act from outside and inside the cell.1,2 Because of the molecular identi—cation of Drosophila TRP,3 func - tional characterizations of recombinant TRP homologues and gene knockout mice have indeed revealed a plethora of stimuli that activate TRP channels (Table 3.1). In addition, respective TRP homologues are susceptible to multiple activation triggers and can function as multimodal sensors. This diversity in activation properties likely contributes to widening the body’s ability to react and adapt to different forms of environmental change by sensing and integrating information. In this chapter, we provide an overview of the activation triggers for mammalian TRP channels and discuss the physiological signi—cance of activation sensitivity. Because we concentrate on “mammalian” TRPs here, readers who are interested in activation of invertebrate TRPs are referred to Chapters 20 and 21 of this book and other excellent reviews.4-6

Stimulation of receptors at the plasma membrane (PM) activates phospholipase C (PLC) via GTP-binding (G) proteins and tyrosine kinases which generates the mes - sengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol-4,5-bisphosphate (PIP2). This induces an elevation of cytosolic Ca2+ concentration, which is controlled by two closely coupled components, IP3-induced Ca2+ release via IP3 receptors (IP3Rs) from the intracellular Ca2+ store, the endoplasmic reticulum (ER), and Ca2+ inŸux across the PM. Association of TRPs with this mode of Ca2+ inŸux has been a major research area, on the basis of the knowledge that PLC-mediated light response is upstream of TRP channels in Drosophila photoreceptor cells.4-6

Interesting protein complexes have been reported for TRP channels such that TRPC3 is associated with the receptor TrkB for brain-derived nerve growth factor.7 In protein

3.7.3 Cold .....................................................................................................65 3.8 Membrane Voltage ..........................................................................................66 3.9 Mechanostimulation ....................................................................................... 67

3.9.1 Membrane Tension.............................................................................. 67 3.9.2 Hypotonicity-Induced Cell Swelling ..................................................68 3.9.3 Hypertonicity-Induced Cell Shrinkage ...............................................68 3.9.4 Shear Stress .........................................................................................68 3.9.5 Mechano-Induced Protein Translocation ...........................................69