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Special Issue "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: 31 July 2021.

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 and Collections in MDPI journals
Dr. Jian Shi
E-Mail
Guest Editor
University Academic Fellow; BHF Intermediate Basic Science Research Fellow; Leeds Institute of Cardiovascular & Metabolic Medicine, School of Medicine, University of Leeds
Interests: Mechanosensation; mechanical sensitivity; shear stress; Piezo1 channels; TRPC channels; endothelial cells; vascular smooth muscle cells; ion channel physiology; ion channel pharmacology; ion channel biophysics

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 papers will be 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 (2 papers)

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Open AccessArticle
Enhanced Shear Force Responsiveness of Epithelial Na+ Channel’s (ENaC) δ Subunit Following the Insertion of N-Glycosylation Motifs Relies on the Extracellular Matrix
Int. J. Mol. Sci. 2021, 22(5), 2500; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052500 - 02 Mar 2021
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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)
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Review

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Open AccessReview
Acid-Sensing Ion Channels and Mechanosensation
Int. J. Mol. Sci. 2021, 22(9), 4810; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094810 - 01 May 2021
Viewed by 273
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)
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