Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

Cell Research, Journal Year: 2015, Volume and Issue: 26(1), P. 83 - 102

Published: Dec. 22, 2015

Language: Английский

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Neural circuits for pain: Recent advances and current views

Science, Journal Year: 2016, Volume and Issue: 354(6312), P. 578 - 584

Published: Nov. 3, 2016

The mammalian nervous system encodes many different forms of pain, from those that arise as a result short-term low-grade interactions with noxious thermal, chemical, or mechanical sources to more serious pain induced by trauma and disease. In this Review, we highlight recent advances in our understanding the neural circuits encode these types pain. Promising therapeutic strategies based on are also highlighted.

Language: Английский

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PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex

Science, Journal Year: 2018, Volume and Issue: 362(6413), P. 464 - 467

Published: Oct. 26, 2018

Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 PIEZO2 are together required baroreception. Genetic ablation both Piezo1 Piezo2 in nodose petrosal sensory ganglia mice abolished drug-induced aortic depressor nerve activity. Awake, behaving animals lack Piezos had labile hypertension increased pressure variability, consistent with phenotypes baroreceptor-denervated humans failure. Optogenetic activation Piezo2-positive afferents was sufficient to initiate mice. These findings suggest long-sought mechanosensors critical control.

Language: Английский

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The Role of PIEZO2 in Human Mechanosensation

New England Journal of Medicine, Journal Year: 2016, Volume and Issue: 375(14), P. 1355 - 1364

Published: Sept. 21, 2016

The senses of touch and proprioception evoke a range perceptions rely on the ability to detect transduce mechanical force. molecular neural mechanisms underlying these sensory functions remain poorly defined. stretch-gated ion channel PIEZO2 has been shown be essential for aspects mechanosensation in model organisms.We performed whole-exome sequencing analysis two patients who had unique neuromuscular skeletal symptoms, including progressive scoliosis, that did not conform standard diagnostic classification. In vitro messenger RNA assays, functional brain imaging, psychophysical kinematic tests were used establish effect genetic variants protein function somatosensation.Each patient carried compound-inactivating PIEZO2, each selective loss discriminative perception but nevertheless responded specific types gentle stimulation hairy skin. profoundly decreased leading ataxia dysmetria markedly worse absence visual cues. However, they perform tasks, such as walking, talking, writing, are considered heavily proprioception.Our results show is determinant humans. (Funded by National Institutes Health Intramural Research Program.).

Language: Английский

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Piezo2 senses airway stretch and mediates lung inflation-induced apnoea

Nature, Journal Year: 2016, Volume and Issue: 541(7636), P. 176 - 181

Published: Dec. 20, 2016

Language: Английский

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Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 15, 2020

Abstract Wolff’s law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict existence a mechanostat links strain induced by forces remodeling. However, how influences remodeling remains elusive. Here, we find Piezo1 deficiency in osteoblastic cells leads loss mass spontaneous fractures with increased resorption. Furthermore, -deficient mice are resistant further resorption hind limb unloading, demonstrating PIEZO1 can affect osteoblast-osteoclast crosstalk response forces. At mechanistic level, loads, controls YAP-dependent expression type II IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify as major mechanosensor tunes homeostasis.

Language: Английский

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Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

eLife, Journal Year: 2015, Volume and Issue: 4

Published: Dec. 8, 2015

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent sensitivity varies substantially across cellular environments, stimulating methods protocols, raising fundamental questions what precise physical stimulus activates channel how its is regulated. Here, we measured currents evoked by membrane stretch three patch configurations, while simultaneously visualizing measuring geometry. Building on this approach, developed protocols minimize resting curvature tension prior probing activity. We find that responds lateral with exquisite as compared other mechanically activated can drive inactivation, thereby tuning overall Piezo1. Our results explain function efficiently adaptable a sensor stimulation diverse contexts.

Language: Английский

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Etiology and Pharmacology of Neuropathic Pain

Pharmacological Reviews, Journal Year: 2018, Volume and Issue: 70(2), P. 315 - 347

Published: March 2, 2018

Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, time-dependent processes, including neuroimmune interactions at peripheral, supraspinal, spinal levels, contribute etiology this "disease pain." Recent work emphasizes roles colony-stimulating factor 1, ATP, brain-derived neurotrophic factor. Excitatory processes are enhanced, inhibitory attenuated in dorsal horn throughout somatosensory system. This leads central sensitization aberrant processing such that tactile innocuous thermal information is perceived as pain (allodynia). Processes involved onset differ from those its long-term maintenance. Opioids display limited effectiveness, less than 35% patients derive meaningful benefit other therapeutic approaches. We thus review promising targets have emerged over last 20 years, Na⁺, K⁺, Ca²⁺, hyperpolarization-activated cyclic nucleotide–gated channels, transient receptor potential channel type V1 adenosine A3 receptors. Despite progress, gabapentinoids retain their status first-line treatments, yet mechanism action poorly understood. outline recent progress understanding show how has provided insights into cellular actions pregabalin gabapentin. Interactions with α2δ-1 subunit voltage-gated Ca²⁺ channels produce multiple neuron type-specific cord higher centers. suggest drugs affect rather a single specific target, greatest promise for future development.

Language: Английский

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A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression

Neuron, Journal Year: 2018, Volume and Issue: 100(4), P. 799 - 815.e7

Published: Oct. 18, 2018

Language: Английский

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Force-induced conformational changes in PIEZO1

Nature, Journal Year: 2019, Volume and Issue: 573(7773), P. 230 - 234

Published: Aug. 21, 2019

Language: Английский

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