Foreword Mechanosensitive Ion Channels, Part B Owen P. Hamill Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas
One of the great challenges in studying mechanotransduction (MT) has been to identify the mechanisms that underlie the exquisite sensitivity and high‐frequency response of specific animal mechanotransducers—a spider detects substrate vibrations within thermal noise limits, whereas a bat generates and detects ultrasounds of frequencies up to 100 kHz in echolocating flying prey. Part B of this volume on mechanosensitive (MS) channels covers the diversity of MS channels and MT mechanisms evident in diVerent invertebrate and vertebrate mechanotransducers. The combined chapters highlight the integration of MS channels into signaling complexes that interact with ancillary structures and other channels that are critical in shaping the specific input–output relations of mechanotransducers. The opening chapters describe MT in the slit sensilla in the spider’s leg, the stretch receptor organ in crayfish muscle, and specific touch receptors in the nematode worm, Caenorhabditis elegans. The studies indicate at least two major channel families, the epithelial Naþ channel (ENaC) and the transient receptor potential (TRP) channels, are involved in MT in lower invertebrates. Subsequent chapters review the roles for ENaC and various TRP channels, and also the MS two‐ pore‐domain Kþ channels and MS voltage‐gated channels in mediating MT in mammalian cells. One of the major hurdles in studying MT has been the absence of specific agents that selectively target MS channels—the potential for the tarantula spider venom peptide GsMTx4 to serve this role is discussed in one chapter. Perhaps one of the interesting actions of GsMTx4 is that it strongly potentiates neurite outgrowth presumably via block of an MS channel that acts as a negative regulator of neurite outgrowth first demonstrated in the leech and reviewed in another chapter. Several chapters highlight diVerent aspects of the most intensely studied of all biological mechanotransducers, namely those mediating vertebrate hearing and touch. These two forms of MT have presented xvii
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the greatest challenge in identifying the membrane proteins forming MS channels, and each chapter provides new information and diVerent approaches that should help in completing this goal. The last part of the volume includes chapters that address the properties of MS channels in cell types where abnormalities in MT contribute to significant human pathologies, including the elevated stretch‐induced Ca2þ influx that contributes to muscle fiber degeneration in muscular dystrophy, abnormalities in the regulation of smooth muscle tone, and baroreception that lead to hypertension, and the alterations in MS channel functional expression that may contribute to increased tumor cell motility and invasion during cancer progression. As indicated in Part A of this volume, I would like to thank Dale Benos for his original invitation to submit the proposal to Elsevier. I would also like to thank all those involved in the production of the volume and, in particular, Phil Carpenter for his continual and patient eVorts during the compilation phase. Finally, I would like to thank all the scientists for presenting their discoveries regarding MS channels.
One of the great challenges in studying mechanotransduction (MT) has been to identify the mechanisms that underlie the exquisite sensitivity and high‐frequency response of specific animal mechanotransducers—a spider detects substrate vibrations within thermal noise limits, whereas a bat generates and detects ultrasounds of frequencies up to 100 kHz in echolocating flying prey. Part B of this volume on mechanosensitive (MS) channels covers the diversity of MS channels and MT mechanisms evident in diVerent invertebrate and vertebrate mechanotransducers. The combined chapters highlight the integration of MS channels into signaling complexes that interact with ancillary structures and other channels that are critical in shaping the specific input–output relations of mechanotransducers. The opening chapters describe MT in the slit sensilla in the spider’s leg, the stretch receptor organ in crayfish muscle, and specific touch receptors in the nematode worm, Caenorhabditis elegans. The studies indicate at least two major channel families, the epithelial Naþ channel (ENaC) and the transient receptor potential (TRP) channels, are involved in MT in lower invertebrates. Subsequent chapters review the roles for ENaC and various TRP channels, and also the MS two‐ pore‐domain Kþ channels and MS voltage‐gated channels in mediating MT in mammalian cells. One of the major hurdles in studying MT has been the absence of specific agents that selectively target MS channels—the potential for the tarantula spider venom peptide GsMTx4 to serve this role is discussed in one chapter. Perhaps one of the interesting actions of GsMTx4 is that it strongly potentiates neurite outgrowth presumably via block of an MS channel that acts as a negative regulator of neurite outgrowth first demonstrated in the leech and reviewed in another chapter. Several chapters highlight diVerent aspects of the most intensely studied of all biological mechanotransducers, namely those mediating vertebrate hearing and touch. These two forms of MT have presented xvii
xviii
Foreword
the greatest challenge in identifying the membrane proteins forming MS channels, and each chapter provides new information and diVerent approaches that should help in completing this goal. The last part of the volume includes chapters that address the properties of MS channels in cell types where abnormalities in MT contribute to significant human pathologies, including the elevated stretch‐induced Ca2þ influx that contributes to muscle fiber degeneration in muscular dystrophy, abnormalities in the regulation of smooth muscle tone, and baroreception that lead to hypertension, and the alterations in MS channel functional expression that may contribute to increased tumor cell motility and invasion during cancer progression. As indicated in Part A of this volume, I would like to thank Dale Benos for his original invitation to submit the proposal to Elsevier. I would also like to thank all those involved in the production of the volume and, in particular, Phil Carpenter for his continual and patient eVorts during the compilation phase. Finally, I would like to thank all the scientists for presenting their discoveries regarding MS channels.
