期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：50
页码：E6955-E6963
DOI：10.1073/pnas.1514138112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceRecordings from Pacinian corpuscles in the 1960s showed that touch elicits symmetric activation followed by rapid adaptation. Sinusoidal stimulation resulted in frequency doubling within a sensitive frequency band, suggesting that these receptors function as frequency-tuned vibration sensors. At the time, the surrounding lamellar capsule was proposed to generate these response dynamics by acting as a mechanical filter. However, similar response dynamics have since been seen in many other mechanoreceptors, leading to controversy over the specificity of this hypothesis. Using a combination of in vivo electrophysiology, feedback-controlled mechanical stimulation, and simulation, we resolve this controversy in favor of a systems-level mechanical filter that is independent of specific anatomical features or specific mechanoelectrical transduction channels. Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities.
