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Expression and function of Piezo channels Multiple tissues and cells express Piezo channels, and each of those shown is discussed in this review. a-e demonstrate the vital role of the Piezo1 channel in the CNS, blood vessels, erythrocytes, lungs, gastrointestinal tract and urinary tract. f-h illustrate the expression of both the Piezo1 channel and Piezo2 channel in articular cartilage, trigeminal ganglia, and dorsal root ganglia. i shows that the Piezo2 channel is expressed in Merkel cells, which are involved in sensing light touch
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Mechanotransduction couples mechanical stimulation with ion flux, which is critical for normal biological processes involved in neuronal cell development, pain sensation, and red blood cell volume regulation. Although they are key mechanotransducers, mechanosensitive ion channels in mammals have remained difficult to identify. In 2010, Coste and co...
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Context 1
... channels are expressed in a wide range of mechanically sensitive cells and allow Ca 2+ influx in response to different types of external forces, such as fluid flow [86], pulling [87], and ultrasonic forces [88]. The biological function of Piezo channels was recently investigated in a number of studies (Fig. 6). The results of these studies verified the pivotal roles of Piezo channels in mechanotransduction under physiological and pathophysiological conditions. Here, we focus on reviewing the biological function of Piezo channels in several different types of MS tissues and ...
Context 2
... Piezo2-conditional deletion in the sensory neurons or in Merkel cells displayed severe deficits in response to gentle touch, but the mechanical nociception sensitivity depending primarily on Aδ and C fibers was unaffected in Piezo2-deficient mice. This provides definitive evidence of the involvement of the Piezo2 channel in touch [158,161,162] (Fig. 6). The Piezo2 channel was found to be present in the sensory endings of proprioceptors, providing the body with the information needed to produce coordinated movement. The critical role of the Piezo2 channel in mediating proprioception was revealed using proprioceptive neuronspecific conditional Piezo2-deleted mice [163]. Together, ...
Citations
... Its mechanosensing activity is influenced by various factors, including ion concentration, fatty acids, lipids, cytoskeleton, and associated proteins such as integrins or other proteins in the plasma membrane [2] or cytosol [3]. Playing a pivotal role in mechanosensing and mechanotransduction [4][5][6][7], Piezo1 significantly contributes to the orchestration of cell functions in both physiological [2,[7][8][9][10][11][12] and pathological [2,13,14] contexts. ...
... Its mechanosensing activity is influenced by various factors, including ion concentration, fatty acids, lipids, cytoskeleton, and associated proteins such as integrins or other proteins in the plasma membrane [2] or cytosol [3]. Playing a pivotal role in mechanosensing and mechanotransduction [4][5][6][7], Piezo1 significantly contributes to the orchestration of cell functions in both physiological [2,[7][8][9][10][11][12] and pathological [2,13,14] contexts. ...
This study sheds light on a ground-breaking biochemical mechanotransduction pathway and reveals how Piezo1 channels orchestrate cell migration. We observed an increased cell migration rate in HEK293T (HEK) cells treated with Yoda1, a Piezo1 agonist, or in HEK cells overexpressing Piezo1 (HEK + P). Conversely, a significant reduction in cell motility was observed in HEK cells treated with GsMTx4 (a channel inhibitor) or upon silencing Piezo1 (HEK-P). Our findings establish a direct correlation between alterations in cell motility, Piezo1 expression, abnormal F-actin microfilament dynamics, and the regulation of Cofilin1, a protein involved in severing F-actin microfilaments.
Here, the conversion of inactive pCofilin1 to active Cofilin1, mediated by the serine/threonine-protein phosphatase 2A catalytic subunit C (PP2AC), resulted in increased severing of F-actin microfilaments and enhanced cell migration in HEK + P cells compared to HEK controls. However, this effect was negligible in HEK-P and HEK cells transfected with hsa-miR-133b, which post-transcriptionally inhibited PP2AC mRNA expression. In summary, our study suggests that Piezo1 regulates cell migration through a biochemical mechanotransduction pathway involving PP2AC-mediated Cofilin1 dephosphorylation, leading to changes in F-actin microfilament dynamics.
... Piezo1, a mechanotransducer, plays a pivotal role in this process. In the Piezo1 ion channel, a specialized transduction structure converts mechanical forces into those used for cation transduction [40]. Therefore, when we inhibited the perception of force by inhibiting the Piezo1 channel, we found that the normal directional migration and self-assembly of cells on the hydrogel were markedly reduced (Figure 2A-H, Movies S2 and S3). ...
Cell-to-cell distant mechanical communication has been demonstrated using in vitro and in vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be fully elucidated. This study further examined the roles of α-Catenin and Piezo1 in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on a Matrigel hydrogel containing type I collagen. Our findings demonstrated that siRNA-mediated downregulation of α-Catenin or Piezo1 expression or chemical inhibition of Piezo1 activity significantly reduced both directional cell movement and branch assembly. Regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA-mediated downregulation of α-Catenin expression caused a marked reduction in focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations imply that mechanosensitive α-Catenin is involved in both cell–cell and cell-matrix adhesions. Additionally, Piezo1 partially localized to Paxillin in focal adhesions, which was inhibited by siRNA-mediated downregulation of α-Catenin expression. This result provides insights into the Piezo1-mediated mechanosensing of traction force on a hydrogel. Collectively, our findings highlight the significance of α-Catenin in the regulation of cell-matrix interactions and provide a possible interpretation of Piezo1-mediated mechanosensing activity at focal adhesions during cell–cell distant mechanical communication.
... This activation can occur through torque exerted by uniform magnetic fields or by pulling membrane sections tethered to nanoparticles in magnetic field gradients [143]. (B) The role of PIEZO channels in human physiology and medical applications [144,145]. (C) Using the Piezo1 channel in magnetogenetics for CRISPR gene editing [93]. (D-E) Stimulation of mechanothermosensitive channels: K2P and TRP. ...
Magnetogenetics emerges as a transformative approach for modulating cellular signaling pathways through the strategic application of magnetic fields and nanoparticles. This technique leverages the unique properties of magnetic nanoparticles (MNPs) to induce mechanical or thermal stimuli within cells, facilitating the activation of mechano- and thermosensitive proteins without the need for traditional ligand-receptor interactions. Unlike traditional modalities that often require invasive interventions and lack precision in targeting specific cellular functions, magnetogenetics offers a non-invasive alternative with the capacity for deep tissue penetration and the potential for targeting a broad spectrum of cellular processes. This review underscores magnetogenetics' broad applicability, from steering stem cell differentiation to manipulating neuronal activity and immune responses, highlighting its potential in regenerative medicine, neuroscience, and cancer therapy. Furthermore, the review explores the challenges and future directions of magnetogenetics, including the development of genetically programmed magnetic nanoparticles and the integration of magnetic field-sensitive cells for in vivo applications. Magnetogenetics stands at the forefront of cellular manipulation technologies, offering novel insights into cellular signaling and opening new avenues for therapeutic interventions.
... Piezo1 channel is one of the so-called "true" mechanosensitive ion channels, which has mechanosensitivity as a major function and which was explored in the last decade [8]. It has one monomer -PIEZO1, three of them together compose a nonselective mechanosensitive channel that conducts mostly cations with a preference for Ca 2+ and Na + with a single-channel conductance of 29 pS [6]. ...
The smooth muscle layer of the urinal bladder (detrusor), along with the urothelium, has autonomous mechanosensitivity and serves as a main sensitive receptor in the organ. Piezo1, together with TREK-1 channel, could play a role of local mechanoreceptors in bladder detrusor smooth muscle (DSM) cells. Piezo1 is a so-called “true” mechanosensitive calcium-permeable ion channel, sensitive to pressure, shear stress, and is activated by pharmacological agonist Yoda1. Using patch-clamp and microfluorescence calcimetry, an unexpected effect from Yoda1 was shown, that is inhibition of rest K+ currents at depolarizing command voltage up to +80 mV. The functional presence of Piezo1 is confirmed by Yoda1-induced rise of intracellular Ca2+ concentration in DSM cells, this was visualized using a Ca2+ sensitive dye Fluo-4 AM, and polymerase cyclic reaction with reverse transcription. In conclusion, Piezo1 channels present in DSM cells and are selectively activated with Yoda1, that causes the inhibition of resting potassium currents.
... The Piezo, known as a mechanotransducer, plays a pivotal role in this process. In the Piezo ion channel, a specialized transduction structure converts mechanical forces into those used for cation transduction [37]. Therefore, when inhibited the perception of force by inhibiting Piezo channel, we found that normal directional migration and self-assembly of cells on the hydrogel was markedly reduced (Figure 2A-E). ...
Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.
... The calcium transient results are largely consistent with the present MEA findings as well as prior work [29,47]. With respect to the whole-cell voltage clamp work, because we measured total current without any channel blockers, the change in reversal potential to more positive potentials is consistent with the Yoda1-induced activation of a cation current with a positive equilibrium potential, aligning with literature reports of PIEZO1 kinetics [48]. Taken together, these data suggest that PIEZO1 is expressed in cortical neurons and is capable of contributing to increased excitability of these networks. ...
PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts.
... Therefore, despite reports regarding Pz1, our results demonstrate colocalization of Pz1 and Pz2 at the HC stereocilia transduction hub in the cochlea and vestibular end-organs. Although sequence homology between Pz1 and Pz2 is~42% 50,51 , analyses of the trimeric interface suggest~84% homology, providing the possibility for hetero-trimeric interaction. We generated non-functional Pz1 and Pz2 knockin (ki) mouse models, floxed at the ROSA26 locus. ...
... The Pz channel consists of trimeric subunits 45 . Pz1 and Pz2 sequences showed~42% homology 50,51 . In contrast to the full-length sequence, the identified Pz1 subunit interface revealed 75% identical and 84% conserved residues with Pz2 (S2-3), which is similar to the heteromeric SK-channel subunit interacting interface that occurs in vitro and in vivo 53 , raising the possibility for hetero-trimeric interaction between Pz1 and Pz2 (see Method for detailed analyses). ...
The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.
... These processes include neuronal growth, axon extension, glial cell migration, regulation of glial cell responsiveness, and the activation of CNS resident immune cells. 6 Moreover, Piezo1 is implicated in neuropathological conditions, such as Alzheimer's disease and brain tumors, showcasing its diverse roles in neuro(patho)physiology. Understanding the basic properties of Piezo1 and its role in the CNS provides valuable insights into the complex interplay between mechanical signals and brain function, opening avenues for potential interventions in central nervous system diseases. ...
... These have shown key roles in proprioception, pain inflection, vascular changes and blood pressure regulation, mediating the mechanotransduction in bone cells, bone development and bone disease 29,30 . The multi tissue effect by piezo proteins can be simply understood by figure 2 58 . During CT/ hijama, suction cups are applied to the skin, near joints or areas of somatic pains, creating a negative pressure. ...
Piezo proteins are ion channel proteins found in various cells of the human body which detect mechanical forces and convert them into electrical signals that can be interpreted by the nervous system. Recent research has shown that these proteins play an important role in a number of physiological processes, including touch sensation, hearing, proliferation, pain modulation and blood pressure regulation. Further research is ongoing to understand the importance of piezo proteins in human health and disease, that could lead to develop the newer therapies for a wide range of conditions. Some physical therapies including Cupping therapy (CT) (Hijama), a well-known regimental therapy in Greco-Arab (Unani) and Chinese medicine, is reported to treat a variety of diseases like, blood pressure and prevents cardiovascular diseases. It is also effective in treating oral and genital ulceration, musculoskeletal pain, nonspecific low back pain, neck pain, fibromyalgia, headache and migraine. Besides various theories hypothesized to explain mechanism of cupping therapy, the piezo protein gates intruded by this therapy may be the best feasible way to understand the mechanism of action of cupping. This novel hypothetical mechanism could pave the way for more researches in medical field especially in chronic ailments. Key words: Cupping, Human Health, Pain, Piezo protein, Unani
... The perspective provided in the current study could offer a unifying viewpoint regarding this debate between Mazur and Pegg and their colleagues. While it is often assumed that the deleterious effect of extracellular ice on cells lies in the adverse effects of mechanical forces acting upon the plasma membrane and disrupting it structurally [56,80,125], it is also possible that these forces induce cation leaks since many ion transport pathways exhibit some mechanosensitivity [29], and it was also observed that mechanical force induces cation leaks and post-hypertonic lysis of human RBCs [114]. ...
... This observation suggests a mechano-sensitivity of cation channels hypothetically involved in cation leaks and post-hypertonic lysis. Generally, many ion channels exhibit mechanosensitivity [29]. In human RBCs, this includes PIEZO1 channels [15,29], transient receptor potential channels TRPC6 [33], and TRPV2 [10,28,92], which are all roughly non-selective for sodium and potassium ions, which makes them possible candidates for facilitating the cation leaks. ...
... Generally, many ion channels exhibit mechanosensitivity [29]. In human RBCs, this includes PIEZO1 channels [15,29], transient receptor potential channels TRPC6 [33], and TRPV2 [10,28,92], which are all roughly non-selective for sodium and potassium ions, which makes them possible candidates for facilitating the cation leaks. Based on the works of Rudenko and Patelaros discussed above [101,106], it might be argued that NMDA receptors [78] could also be involved in hypertonicity-related cation leaks. ...
Human red blood cells (RBC) exposed to hypertonic media are subject to post-hypertonic lysis - an injury that only develops during resuspension to an isotonic medium. The nature of post-hypertonic lysis was previously hypothesized to be osmotic when cation leaks were observed, and salt loading was suggested as a cause of the cell swelling upon resuspension in an isotonic medium. However, it was problematic to account for the salt loading since the plasma membrane of human RBCs was considered impermeable to cations. In this study, the hypertonicity-related behavior of human RBCs is revisited within the framework of modern cell physiology, considering current knowledge on membrane ion transport mechanisms - an account still missing. It is recognized here that the hypertonic behavior of human RBCs is consistent with the acute regulatory volume increase (RVI) response – a healthy physiological reaction initiated by cells to regulate their volume by salt accumulation. It is shown by reviewing the published studies that human RBCs can increase cation conductance considerably by activating cell volume-regulated ion transport pathways inactive under normal isotonic conditions and thus facilitate salt loading. A simplified physiological model accounting for transmembrane ion fluxes and membrane voltage predicts the isotonic cell swelling associated with increased cation conductance, eventually reaching hemolytic volume. The proposed involvement of cell volume regulation mechanisms shows the potential to explain the complex nature of the osmotic response of human RBCs and other cells. Cryobiological implications, including mechanisms of cryoprotection, are discussed.
