The Piezo2 ion channel is mechanically activated by low-threshold positive pressure

Shin, Kyeong‐Cheol; Park, Hyun Ji; Kim, Jae Gon; Lee, In Hwa; Cho, Hawon; Park, Chanjae; Sung, Tae Sik; Koh, Sang Don; Park, Sang Woong; Bae, Young Min

doi:10.1038/s41598-019-42492-4

Cited by 40 publications

(33 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3a). These mechano-currents have been shown to be mediated by PIEZO2 2,3,40 . As with our experiments using transiently transfected N2A cells, MA supplementation in MCC13 decreased endogenous PIEZO2 currents (Fig.…”

Section: Resultsmentioning

confidence: 99%

A dietary fatty acid counteracts neuronal mechanical sensitization

et al. 2020

View full text Add to dashboard Cite

PIEZO2 is the essential transduction channel for touch discrimination, vibration, and proprioception. Mice and humans lacking Piezo2 experience severe mechanosensory and proprioceptive deficits and fail to develop tactile allodynia. Bradykinin, a proalgesic agent released during inflammation, potentiates PIEZO2 activity. Molecules that decrease PIEZO2 function could reduce heightened touch responses during inflammation. Here, we find that the dietary fatty acid margaric acid (MA) decreases PIEZO2 function in a dose-dependent manner. Chimera analyses demonstrate that the PIEZO2 beam is a key region tuning MAmediated channel inhibition. MA reduces neuronal action potential firing elicited by mechanical stimuli in mice and rat neurons and counteracts PIEZO2 sensitization by bradykinin. Finally, we demonstrate that this saturated fatty acid decreases PIEZO2 currents in touch neurons derived from human induced pluripotent stem cells. Our findings report on a natural product that inhibits PIEZO2 function and counteracts neuronal mechanical sensitization and reveal a key region for channel inhibition.

show abstract

Section: Resultsmentioning

confidence: 99%

A dietary fatty acid counteracts neuronal mechanical sensitization

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Piezo1 is activated by both negative or positive pressure applied in the cell-attached patch clamp configuration (Coste et al, 2010). By contrast, Piezo2 opens in response to positive, but not negative, pressure (Shin et al, 2019).…”

Section: The Low Threshold Cationic Non-selective Piezo1 Channel Is Imentioning

confidence: 99%

Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Douguet

Honoré

2019

Cell

145

128

View full text Add to dashboard Cite

The conversion of force into an electrical cellular signal is mediated by the opening of different types of mechanosensitive ion channels (MSCs), including TREK/TRAAK K 2P channels, Piezo1/2, TMEM63/OSCA and TMC1/2. Mechanoelectrical transduction plays a key role in hearing, balance, touch, proprioception and is also implicated in the autonomic regulation of blood pressure and breathing. Thus, dysfunction of MSCs is associated with a variety of inherited and acquired disease states. Significant progress has recently been made in identifying these channels, solving their structure and understanding the gating of both hyperpolarizing and depolarizing MSCs. Besides prototypical activation by membrane tension, additional gating mechanisms involving channel curvature and/or tethered elements are at play.

show abstract

“…In general, mechano-nociceptors only fire when a mechanical stimulus is applied or removed in a phasic way (Belmonte et al, 1991 ; MacIver and Tanelian, 1993b ). Piezo2, a long transmembrane protein and non-selective cation channel mechanically activated (Coste et al, 2010 ; Shin et al, 2019 ), has emerged as a marker of mechano-nociceptors in primary sensory neurons.…”

Section: Functional Classification Of Corneal Fibersmentioning

confidence: 99%

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

Guerrero-Moreno

Baudouin

Mélik-Parsadaniantz

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.

show abstract

The Piezo2 ion channel is mechanically activated by low-threshold positive pressure

Cited by 40 publications

References 13 publications

A dietary fatty acid counteracts neuronal mechanical sensitization

A dietary fatty acid counteracts neuronal mechanical sensitization

Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

Contact Info

Product

Resources

About