Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Mechanosensitive Ion Channels in Health and Disease
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Mechanosensitive Ion Channels in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 25084

Special Issue Editors

Prof. Dr. Rashid Giniatullin

E-Mail Website
Guest Editor
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Neulaniementie 2, 70211 Kuopio, Finland
Interests: synaptic transmission; neuronal plasticity; neuron-glia interactions; neuronal networks; purinergic mechanisms; mechanosensitive ion channels; neurotransmitter receptors in health and disease; receptor desensitization; receptor trafficking; modelling of receptor kinetics; mitochondria; reactive oxygen species; molecular and cellular mechanisms of pain and analgesia; migraine; neuroprotection
Special Issues, Collections and Topics in MDPI journals
Dr. Jian Shi

E-Mail Website
Guest Editor
Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
Interests: ion channel physiology; ion channel pharmacology; ion channel biophysics; electrophysiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mechanic sensitivity is the fundamental aspect of functioning of all living species. The still intriguing issue is the nature of the special sensors for detection of mechanical forces. For long time the sensitivity to mechanical forces was attributed to different types of membrane proteins ranging from NMDA glutamate receptors to different subtypes of potassium or TRP channels.  

After discovery in 2010, this list was extended as Piezo channels have emerged as the most sensitive mechanotransducers implicated in a huge variety of physiological and pathological functions. These extremely ‘heavy’ proteins are expressed in sensory neurons to detect the touch and implicated in hearing; in endothelial cells, Piezo1 channels sense shear stress to dictate many important functions such as embryonic development, regulation of vascular tone, angiogenesis and atherosclerosis progression;  in red blood cells they serve as the sensors of the shear stress and are closely linked to red blood cell diseases; in myeloid cells Piezo1 channels are essential for innate immunity; in baroreceptors Piezo1 and Piezo2 channels sense blood pressure; in astrocytes they potentially implicated in the development of Alzheimer’s Disease. Notably, apart from natural mechanical forces, Piezo1 channels are sensitive to the chemical agonist, Yoda1. However, the endogenous Piezo1 agonists are not found yet. 

Activation of Piezo channels is tightly coupled to the purinergic signalling as ATP release is extremely sensitive to mechanical stress suggesting an interesting synergy between these two singlling systems.

One issue of high translational importance in view of the coronavirus pandemics, is the role of Piezo channels in lungs as the data on their functional effects in this tissue are very contradictory. Likewise, the contradictory is the role of Piezo channels in cancer development.

This Special Issue ' Mechanosensitive Ion Channels in Health and Disease ' aims to collect reviews and original papers related to the basic functions of different types of mechanosensitive ion channels and translational aspects of these transducers of mechanical forces.

Prof. Dr. Rashid Giniatullin
Dr. Jian Shi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mechanobiology
  • mechanical sensitivity
  • Piezo channels
  • TRP channels
  • K2P channels
  • Yoda1
  • substrate mechanics
  • stretching
  • shear stress
  • extracellular matrix

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

13 pages, 6329 KiB  
Communication
Functional Characterization of Mechanosensitive Piezo1 Channels in Trigeminal and Somatic Nerves in a Neuron-on-Chip Model
by Nikita Mikhailov, Lidiia Plotnikova, Prateek Singh, Rashid Giniatullin and Riikka H. Hämäläinen
Int. J. Mol. Sci. 2022, 23(3), 1370; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031370 - 25 Jan 2022
Cited by 12 | Viewed by 3955
Abstract
Mechanosensitive ion channels, Piezo1 and 2, are activated by pressure and involved in diverse physiological functions, including senses of touch and pain, proprioception and many more. Understanding their function is important for elucidating the mechanosensitive mechanisms of a range of human diseases. Recently, [...] Read more.
Mechanosensitive ion channels, Piezo1 and 2, are activated by pressure and involved in diverse physiological functions, including senses of touch and pain, proprioception and many more. Understanding their function is important for elucidating the mechanosensitive mechanisms of a range of human diseases. Recently, Piezo channels were suggested to be contributors to migraine pain generation. Migraine is typically characterized by allodynia and mechanical hyperalgesia associated with the activation and sensitization of trigeminal ganglion (TG) nerve fibers. Notably, migraine specific medicines are ineffective for other types of pain, suggesting a distinct underlying mechanism. To address, in a straightforward manner, the specificity of the mechanosensitivity of trigeminal vs. somatic nerves, we compared the activity of Piezo1 channels in mouse TG neurons vs. dorsal root ganglia (DRG) neurons. We assessed the functional expression of Piezo1 receptors using a conventional live calcium imaging setup equipped with a multibarrel application system and utilizing a microfluidic chip-based setup. Surprisingly, the TG neurons, despite higher expression of the Piezo1 gene, were less responsive to Piezo1 agonist Yoda1 than the DRG neurons. This difference was more prominent in the chip-based setup, suggesting that certain limitations of the conventional approach, such as turbulence, can be overcome by utilizing microfluidic devices with laminar solution flow. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

13 pages, 3862 KiB  
Article
Enhanced Shear Force Responsiveness of Epithelial Na+ Channel’s (ENaC) δ Subunit Following the Insertion of N-Glycosylation Motifs Relies on the Extracellular Matrix
by Daniel Barth, Fenja Knoepp and Martin Fronius
Int. J. Mol. Sci. 2021, 22(5), 2500; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052500 - 02 Mar 2021
Cited by 6 | Viewed by 2009
Abstract
Members of the Degenerin/epithelial Na+ channel (ENaC) protein family and the extracellular cell matrix (ECM) form a mechanosensitive complex. A core feature of this complex are tethers, which connect the channel with the ECM, however, knowledge about the nature of these tethers [...] Read more.
Members of the Degenerin/epithelial Na+ channel (ENaC) protein family and the extracellular cell matrix (ECM) form a mechanosensitive complex. A core feature of this complex are tethers, which connect the channel with the ECM, however, knowledge about the nature of these tethers is scarce. N-glycans of α ENaC were recently identified as potential tethers but whether N-glycans serve as a ubiquitous feature for mechanosensation processes remains unresolved. The purpose of this study was to reveal whether the addition of N-glycans to δ ENaC—which is less responsive to shear force (SF)—increases its SF-responsiveness and whether this relies on a linkage to the ECM. Therefore, N-glycosylation motifs were introduced via site-directed mutagenesis, the resulting proteins expressed with β and γ ENaC in Xenopus oocytes, and SF-activated currents measured by two-electrode voltage-clamp. The insertion of N-glycosylation motifs increases δ ENaC’s SF responsiveness. The inclusion of a glycosylated asparagine (N) at position 487 did increase the molecular mass and provided a channel whose SF response was abolished following ECM degradation via hyaluronidase. This indicates that the addition of N-glycans improves SF-responsiveness and that this effect relies on an intact ECM. These findings further support the role of N-glycans as tethers for mechanotransduction. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

13 pages, 1156 KiB  
Review
The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration
by Annalisa Bernareggi, Alessandra Bosutti, Gabriele Massaria, Rashid Giniatullin, Tarja Malm, Marina Sciancalepore and Paola Lorenzon
Int. J. Mol. Sci. 2022, 23(12), 6616; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126616 - 14 Jun 2022
Cited by 8 | Viewed by 4321
Abstract
Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, [...] Read more.
Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, with a particular focus on the role of Piezo1 in controlling myogenic precursor activity and skeletal muscle regeneration and vascularization. The disclosed effects reported by pharmacological activation of Piezo1 channels with the selective agonist Yoda1 indicate a potential impact of Piezo1 channel activity in skeletal muscle regeneration, which is disrupted in various muscular pathological states. All findings reported so far agree with the idea that Piezo1 channels represent a novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating skeletal muscle disorders characterized by an impairment of tissue regenerative potential. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

27 pages, 1834 KiB  
Review
Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels
by Miklós Lengyel, Péter Enyedi and Gábor Czirják
Int. J. Mol. Sci. 2021, 22(16), 9062; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22169062 - 23 Aug 2021
Cited by 8 | Viewed by 2759
Abstract
The two-pore domain K2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K2P subunits encoded by the KCNK genes, the three members of the [...] Read more.
The two-pore domain K2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K2P subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K+ current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions. In the past decade, great advances have been made in the investigation of the molecular determinants of mechanosensation, and members of the TREK subfamily have emerged among the best-understood examples of mammalian ion channels directly influenced by the tension of the phospholipid bilayer. In parallel, the crucial contribution of mechano-gated TREK channels to the regulation of membrane potential in several cell types has been reported. In this review, we summarize the general principles underlying the mechanical activation of K2P channels, and focus on the physiological roles of mechanically induced hyperpolarization. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

18 pages, 470 KiB  
Review
Cross-Talk between Mechanosensitive Ion Channels and Calcium Regulatory Proteins in Cardiovascular Health and Disease
by Yaping Wang, Jian Shi and Xiaoyong Tong
Int. J. Mol. Sci. 2021, 22(16), 8782; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168782 - 16 Aug 2021
Cited by 17 | Viewed by 3212
Abstract
Mechanosensitive ion channels are widely expressed in the cardiovascular system. They translate mechanical forces including shear stress and stretch into biological signals. The most prominent biological signal through which the cardiovascular physiological activity is initiated or maintained are intracellular calcium ions (Ca2+ [...] Read more.
Mechanosensitive ion channels are widely expressed in the cardiovascular system. They translate mechanical forces including shear stress and stretch into biological signals. The most prominent biological signal through which the cardiovascular physiological activity is initiated or maintained are intracellular calcium ions (Ca2+). Growing evidence show that the Ca2+ entry mediated by mechanosensitive ion channels is also precisely regulated by a variety of key proteins which are distributed in the cell membrane or endoplasmic reticulum. Recent studies have revealed that mechanosensitive ion channels can even physically interact with Ca2+ regulatory proteins and these interactions have wide implications for physiology and pathophysiology. Therefore, this paper reviews the cross-talk between mechanosensitive ion channels and some key Ca2+ regulatory proteins in the maintenance of calcium homeostasis and its relevance to cardiovascular health and disease. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

16 pages, 1211 KiB  
Review
Acid-Sensing Ion Channels and Mechanosensation
by Nina Ruan, Jacob Tribble, Andrew M. Peterson, Qian Jiang, John Q. Wang and Xiang-Ping Chu
Int. J. Mol. Sci. 2021, 22(9), 4810; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094810 - 01 May 2021
Cited by 38 | Viewed by 4679
Abstract
Acid-sensing ion channels (ASICs) are mainly proton-gated cation channels that are activated by pH drops and nonproton ligands. They are part of the degenerin/epithelial sodium channel superfamily due to their sodium permeability. Predominantly expressed in the central nervous system, ASICs are involved in [...] Read more.
Acid-sensing ion channels (ASICs) are mainly proton-gated cation channels that are activated by pH drops and nonproton ligands. They are part of the degenerin/epithelial sodium channel superfamily due to their sodium permeability. Predominantly expressed in the central nervous system, ASICs are involved in synaptic plasticity, learning/memory, and fear conditioning. These channels have also been implicated in multiple disease conditions, including ischemic brain injury, multiple sclerosis, Alzheimer’s disease, and drug addiction. Recent research has illustrated the involvement of ASICs in mechanosensation. Mechanosensation is a form of signal transduction in which mechanical forces are converted into neuronal signals. Specific mechanosensitive functions have been elucidated in functional ASIC1a, ASIC1b, ASIC2a, and ASIC3. The implications of mechanosensation in ASICs indicate their subsequent involvement in functions such as maintaining blood pressure, modulating the gastrointestinal function, and bladder micturition, and contributing to nociception. The underlying mechanism of ASIC mechanosensation is the tether-gate model, which uses a gating-spring mechanism to activate ASIC responses. Further understanding of the mechanism of ASICs will help in treatments for ASIC-related pathologies. Along with the well-known chemosensitive functions of ASICs, emerging evidence has revealed that mechanosensitive functions of ASICs are important for maintaining homeostasis and contribute to various disease conditions. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

9 pages, 1633 KiB  
Brief Report
Selective Chemical Activation of Piezo1 in Leukemia Cell Membrane: Single Channel Analysis
by Valeria Vasileva, Elena Morachevskaya, Anastasia Sudarikova, Yuri Negulyaev and Vladislav Chubinskiy-Nadezhdin
Int. J. Mol. Sci. 2021, 22(15), 7839; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157839 - 22 Jul 2021
Cited by 6 | Viewed by 2632
Abstract
Piezo1/2 are mechanosensitive calcium-permeable channels that can be activated by various modes of membrane deformation. The identification of the small molecule Yoda1, a synthetic Piezo1 agonist, revealed the possibility of chemical activation of the channel. Stimulating effects of Yoda1 on Piezo1 have been [...] Read more.
Piezo1/2 are mechanosensitive calcium-permeable channels that can be activated by various modes of membrane deformation. The identification of the small molecule Yoda1, a synthetic Piezo1 agonist, revealed the possibility of chemical activation of the channel. Stimulating effects of Yoda1 on Piezo1 have been mainly documented using over-expressing cellular systems or channel proteins incorporated in artificial lipid bilayers. However, the activating effect of Yoda1 on native Piezo1 channels in the plasma membrane of living cells remains generally undefined, despite the increasing number of studies in which the agonist is utilized as a functional tool to reveal the contribution of Piezo1 to cellular reactions. In the current study, we used the human myeloid leukemia K562 cell line as a suitable model to examine chemically induced Piezo1 activity with the use of the patch-clamp technique in various specific modes. The functional expression of Piezo1 in leukemia cells was evidenced using a combinative approach, including single channel patch-clamp measurements. Utilizing our established single-current whole-cell assay on K562 cells, we have shown, for the first time, the selective real-time chemical activation of endogenously expressed Piezo1. Extracellular application of 0.5–1 µM Yoda1 effectively stimulated single Piezo1 currents in the cell membrane. Full article
(This article belongs to the Special Issue Mechanosensitive Ion Channels in Health and Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop