Key Points
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Mechanotransduction, the conversion of a mechanical stimulus into a biological response, constitutes the basis of fundamental physiological processes, including the senses of touch and pain.
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In mammals, detection of mechanical forces by the somatosensory system is performed by primary afferent neurons that project long axons to the skin and to deeper body structures. Cutaneous mechanoreceptors are specialized to detect a wide range of mechanical stimuli including light brush of the skin, texture, vibration, touch and noxious pressure.
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The ability of these mechanoreceptors to detect mechanical cues relies on the presence of mechanosensitive channels on the sensory nerve endings that rapidly transform mechanical forces into electrical signals.
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Although it has been remarkably difficult to characterize mechanotranducer channels at the molecular level, recent studies have provided insights into the basic properties and molecular identities of mechanosensitive channels in mammalian sensory neurons.
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Such analyses suggest that mechanical stimulation activates cation channels that differ in their sensitivity to pressure and desensitization rates, and that may define different classes of mechanotransducer channels.
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Although the molecular characterization of mechanosensitive channels remains uncertain, recent studies suggest that transient receptor potential cation channel ankyrin1 (TRPA1) as well as piezo proteins contribute to the mechanotranducer apparatus in mammalian sensory neurons.
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Molecular identification of transducer channels will undoubtedly accelerate our understanding of mechanotransduction in mammals and of its impairments in disease and post-traumatic states.
Abstract
The somatosensory system mediates fundamental physiological functions, including the senses of touch, pain and proprioception. This variety of functions is matched by a diverse array of mechanosensory neurons that respond to force in a specific fashion. Mechanotransduction begins at the sensory nerve endings, which rapidly transform mechanical forces into electrical signals. Progress has been made in establishing the functional properties of mechanoreceptors, but it has been remarkably difficult to characterize mechanotranducer channels at the molecular level. However, in the past few years, new functional assays have provided insights into the basic properties and molecular identity of mechanotransducer channels in mammalian sensory neurons. The recent identification of novel families of proteins as mechanosensing molecules will undoubtedly accelerate our understanding of mechanotransduction mechanisms in mammalian somatosensation.
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Acknowledgements
The data adapted to create the model in Figure 5a and the piezo recordings in figure 5d are kindly provided by B. Coste and A. Patapoutian. This study was supported by the Centre National de la Recherche Scientifique (CNRS) and by grants from the Agence Nationale de la Recherche, Fondation Schlumberger, ARCInca-2006, Institut UPSA de la Douleur, Institut pour la Recherche sur la Moelle Épinière et l'Encéphale (IRME) and Fondation pour la Recherche Médicale.
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Glossary
- Mechanoreceptor
-
A sensory receptor that responds to mechanical pressure or distortion by causing membrane depolarization and action potential firing.
- Mechanotransducer channel
-
An ion channel present in the cell membranes of prokaryotes and eukaryotes, capable of generating an ion flux signal as a response to mechanical stimuli.
- Desensitization
-
The loss of responsiveness to the continuing presence of a stimulus.
- A-fibre
-
An afferent myelinated fibre of large (Aβ) or medium (Aδ) diameter.
- C-fibre
-
An afferent unmyelinated fibre of small diameter conveying input signals with a slow conduction velocity.
- Neurite
-
Any projection from the cell body of a neuron, which can be either an axon or a dendrite.
- Latency
-
The delay between a stimulus and the response it triggers.
- Half-activation midpoint
-
The intensity of a stimulus that induces a half-maximal response.
- Reversal potential
-
The membrane potential at which the net ion current flow becomes zero.
- Randall–Selitto test
-
A technique for the measurement of pain response in animals by observing the reaction to gradually increasing pressure on a paw.
- Von Frey hairs
-
A range of filaments of varying diameters that are used to exert a calibrated pressure on an animal's paw.
- Allodynia
-
Pain due to a stimulus that does not normally provoke pain.
- Inactivation
-
The process by which and ion channel enters a refractory state following activation. Reactivation to the conductive state cannot occur until inactivation is removed.
- Baroreceptor
-
A type of mechanoreceptor that detects the pressure of blood flowing past and sends messages to the CNS.
- Hyperalgesia
-
A heightened sensitivity to a painful stimulus.
- Chordotonal ciliary tips
-
Sensory cilia of stretch receptor organs in insects and other arthropods.
- Crenation
-
Cell shrinkage after exposure to a hypertonic solution.
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Delmas, P., Hao, J. & Rodat-Despoix, L. Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat Rev Neurosci 12, 139–153 (2011). https://doi.org/10.1038/nrn2993
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DOI: https://doi.org/10.1038/nrn2993
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