Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

Lengyel, M; Enyedi, Péter; Czirják, Gábor

doi:10.3390/ijms22169062

Cited by 13 publications

(9 citation statements)

References 192 publications

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“…For the moment, we cannot exclude the role of other cellular machinery since ultrasound neuromodulatory effects were not fully eliminated in the P1KO neurons. Previous studies have shown that some TRP channels such as TRPA1, TRPP1/2, TRPC1, TRPV1 (Burks et al ., 2019; Oh et al ., 2019; Yang et al ., 2021; Yoo et al ., 2022), potassium channel such as TREK1 and TRAAK (Lengyel et al ., 2021; Sorum et al ., 2021), and calcium voltage-gated channels (VGCs) (Arnadottir & Chalfie, 2010; Tyler, 2012), may also contribute to the ultrasound induced neural activity. We agree with these findings that other ion channels in difference cell type, astrocyte(Oh et al ., 2019) for example, may contribute to the ultrasound neuromodulation, especially under high ultrasound acoustic pressure.…”

Section: Discussionmentioning

confidence: 99%

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Zhu

Xian

Hou

et al. 2023

Preprint

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Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of non-invasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1, was studied through a conditional knockout mouse model as a major molecule for ultrasound neuromodulation ex vivo and in vivo. We showed that Piezo1 knockout in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement and muscle EMG responses. We also detected higher Piezo1 in the central amygdala (CEA) which were found more sensitive to ultrasound stimulation than that of cortex. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation while knocking out astrocytic Piezo1 showed no obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory cortical activation and using smooth waveform ultrasound with randomized parameters to stimulate P1KO ipsilateral and contralateral regions of the same brain and recording evoked movement in the corresponding limb. Thus, we demonstrate that Piezo1 is functionally expressed in different brain regions, and that it is an important mediator of ultrasound neuromodulation in the brain, laying the ground for further mechanistic studies of ultrasound.

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Section: Discussionmentioning

confidence: 99%

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Zhu

Xian

Hou

et al. 2023

Preprint

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“…For example, the TREK subfamily protein changes its structure and passes K + ions. It is well-known that lateral forces acting on the channel protein are the most important to causing gate transition [45,46] and are produced by the stretch, bending, shearing, torsion, and local effects of the channel protein [45]. Although hydrostatic pressure is not included in these forces, hydrostatic pressure might also affect the changes in lateral force (or strains).…”

Section: Discussionmentioning

confidence: 99%

Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation

Zamri

Ujihara

Nakamura

et al. 2022

IJMS

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In response to hydrostatic pressure, the cation channel transient receptor potential vanilloid 1 (TRPV1) is essential in signaling pathways linked to glaucoma. When activated, TRPV1 undergoes a gating transition from a closed to an open state that allows the influx of Ca2+ ions. However, the gating mechanism of TRPV1 in response to hydrostatic pressure at the molecular level is still lacking. To understand the effect of hydrostatic pressure on the activation of TRPV1, we conducted molecular-dynamics (MD) simulations on TRPV1 under different hydrostatic pressure configurations, with and without a cell membrane. The TRPV1 membrane-embedded model is more stable than the TPRV1-only model, indicating the importance of including the cell membrane in MD simulation. Under elevated pressure at 27.6 mmHg, we observed a more dynamic and outward motion of the TRPV1 domains in the lower-gate area than in the simulation under normal pressure at 12.6 mmHg. While a complete closed-to-open-gate transition was not evident in the limited course of our MD simulations, an increase in the channel radius at the lower gate was observed at 27.6 mmHg versus that at 12.6 mmHg. These findings provide novel information regarding the effect of hydrostatic pressure on TRPV1 channels.

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“…Important also to note that Piezo and K2P channels are putative mechanosensitive channels, meaning that they are primarily mechanically gated channels that act as the specific force sensors themselves [ 107 – 109 ], while TRP, ASICs and NMDA channels are likely primarily designed to react to other specific stimuli making their mechanical sensitivity a “second profession”. As for glutamate NMDA receptors, in this review, we limited discussion on the role of NMDA channels to their pure mechanosensitive role while they play a key contribution to CSD underlying migraine aura [ 110 ] and participate in transmission of nociceptive stimuli.…”

Section: Methodsmentioning

confidence: 99%

Mechanosensitive receptors in migraine: a systematic review

Della Pietra,

Gómez Dabó,

Mikulenka

et al. 2024

J Headache Pain

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Background Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. Methods A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. Results We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. Conclusions Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

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Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

Cited by 13 publications

References 192 publications

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation

Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation

Mechanosensitive receptors in migraine: a systematic review

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