Key Points
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Although many ion channels are implicated in mechanosensation, it is hard to be sure that such channels are directly gated by mechanical force. Criteria that help to establish direct gating include specific tests such as: does mechanosensation involve direct activation of a channel? does the candidate protein participate in mechanical transduction? is the candidate protein mechanically sensitive? is the candidate protein a pore-forming subunit? and is the candidate protein a force-sensing subunit?
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Various transient receptor potential (TRP) channels are involved in mechanosensation in non-neural cells — including TRPC1 in oocytes, TRPC3 and TRPC6 in myogenic tone, TRPV1 in bladder, PKD1 and PKD2 in flow-sensing in kidney and TRPV4 in osmosensing. It is difficult to establish direct gating for most of these, partly because the stimuli are slow; evidence suggests that many of them are activated by second messengers.
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Forward genetics has revealed a role for TRP channels in Caenorhabditis elegans mechanosensation, specifically, for the worm homologues of PKD1 and PKD2 in male sensation of vulva location and for OSM-9 and OCR-2 in nose touch and osmosensation. Remarkably, the vertebrate TRPV4 can rescue mutations in the worm OSM-9, when expressed in worm sensory neurons.
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The ability of Drosophila melanogaster to respond to painful heat and touch stimuli involves painless, a TRP channel expressed in multidendritic neurons, and TRPN1, a bristle deflection sensor. Bristle deflection almost certainly involves a directly gated channel, which may be TRPN1 itself.
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Three TRP channels (TRPN1, Nanchung and Inactive) are required for proper hearing in Drosophila, a process that involves mechanosensation of the sound-evoked rotation of the antenna, but it is not clear which is the direct sensor and which have the necessary supporting roles.
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A variety of TRP channels that sense sound and head movements are expressed by hair cells of the vertebrate inner ear; these include TRPV4, TRPML3 and TRPA1. There is some evidence that supports a role for each of them in mechanosensation, but there is more evidence that casts doubt on a direct involvement. At present there is no good candidate for the hair-cell transduction channel.
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The short latency of the receptor current in vertebrate touch and proprioceptive neurons suggests direct gating of a still unidentified mechanosensory channel. One TRP channel, TRPA1, is involved in sensing painful mechanical stimuli but it may be activated downstream of the true force sensor or simply control the environment of the true transduction channel.
Abstract
Ion channels of the transient receptor potential (TRP) superfamily are involved in a wide variety of neural signalling processes, most prominently in sensory receptor cells. They are essential for mechanosensation in systems ranging from fruitfly hearing, to nematode touch, to mouse mechanical pain. However, it is unclear in many instances whether a TRP channel directly transduces the mechanical stimulus or is part of a downstream signalling pathway. Here, we propose criteria for establishing direct mechanical activation of ion channels and review these criteria in a number of mechanosensory systems in which TRP channels are involved.
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-
A homeostatic mechanism by which cells maintain their volume despite changes in extracellular osmolarity.
- Liposome
-
A lipid vesicle that is artificially formed by sonicating lipids in an aqueous solution.
- Heterologous expression system
-
A system for studying the function of a protein in which a gene construct is transfected into suitable host cells such as bacteria or cultured mammalian cells that will produce the protein in a near-native environment.
- Merkel cell
-
A specialized cell in the skin, often associated with sensory hairs, that is involved in cutaneous mechanosensation.
- Circumventricular organ
-
A region of the brain that has a rich vascular plexus with a specialized arrangement of blood vessels. The junctions between the capillary endothelial cells are not tight in the blood vessels of these regions, allowing the diffusion of large molecules.
- Johnston's organ
-
The hearing organ in insects, formed by a collection of mechanosensory neurons in the second antennal segment that respond to sound-induced rotation of the third antennal segment.
- Arista
-
A feathery appendage of the insect antenna that is moved by acoustic stimuli.
- Chordotonal organ
-
A sensory organ in insects that detects mechanical and sound vibrations.
- Stereocilia
-
Elongated microvilli emanating from the apical surfaces of hair cells, composed of a dense core of crosslinked actin filaments surrounded by the cell membrane.
- Endolymph
-
The fluid filling the scala media of the cochlea and the lumen of the vestibular organs. Endolymph has an unusual ion composition with high potassium and low sodium concentrations.
- Morpholinos
-
Antisense oligonucleotides that block gene expression by interfering with the translation initiation complex or with RNA splicing.
- Kinocilia
-
A single true cilium containing microtubules that emanates from the apical surfaces of hair cells, adjacent to the tallest stereocilia.
- Utricle
-
One of three types of vertebrate vestibular organs (along with the saccule and semicircular canals) that is sensitive to linear acceleration.
- Microphonic potential
-
An extracellular receptor potential from inner ear organs caused by current flowing through receptor cells. Like a microphone, the cochlea produces a small voltage in response to acoustic stimuli.
- Slowly adapting neuron
-
Sensory neuron that maintains firing for the duration of a stimulus.
- Rapidly adapting neuron
-
Sensory neuron that fires at the start of a sensory stimulus but shows a decay, or adaptation, of firing during maintained stimuli.
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Christensen, A., Corey, D. TRP channels in mechanosensation: direct or indirect activation?. Nat Rev Neurosci 8, 510–521 (2007). https://doi.org/10.1038/nrn2149
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DOI: https://doi.org/10.1038/nrn2149
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