Cross-Talk between Mechanosensitive Ion Channels and Calcium Regulatory Proteins in Cardiovascular Health and Disease

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.

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Ion Channels in Epithelial Dynamics and Morphogenesis

Cells ◽

10.3390/cells10092280 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2280

Author(s):

Ankit Roy Choudhury ◽

Jörg Großhans ◽

Deqing Kong

Keyword(s):

Nervous System ◽

Ion Channels ◽

Epithelial Cells ◽

Cell Types ◽

Mechanical Forces ◽

Morphogenetic Movements ◽

Mechanosensitive Ion Channels ◽

Channel Proteins ◽

Epithelial Tissues

Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain. Recent studies point to a function of these channel proteins in cell types and tissues in addition to the nervous system, such as epithelia, where they have been little studied, and their role has remained elusive. Dynamic epithelia are intrinsically exposed to mechanical forces. A response to pull and push is assumed to constitute an essential part of morphogenetic movements of epithelial tissues, for example. Mechano-gated channels may participate in sensing and responding to such forces. In this review, focusing on Drosophila, we highlight recent results that will guide further investigations concerned with the mechanistic role of these ion channels in epithelial cells.

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Selective activation of mechanosensitive ion channels using magnetic particles

Journal of The Royal Society Interface ◽

10.1098/rsif.2007.1274 ◽

2007 ◽

Vol 5 (25) ◽

pp. 855-863 ◽

Cited By ~ 109

Author(s):

Steven Hughes ◽

Stuart McBain ◽

Jon Dobson ◽

Alicia J El Haj

Keyword(s):

Ion Channels ◽

Ion Channel ◽

Magnetic Particles ◽

Channel Structure ◽

Biological Research ◽

Mechanical Forces ◽

Extracellular Loop ◽

Whole Cell ◽

Mechanosensitive Ion Channels ◽

Loop Region

This study reports the preliminary development of a novel magnetic particle-based technique that permits the application of highly localized mechanical forces directly to specific regions of an ion-channel structure. We demonstrate that this approach can be used to directly and selectively activate a mechanosensitive ion channel of interest, namely TREK-1. It is shown that manipulation of particles targeted against the extended extracellular loop region of TREK-1 leads to changes in whole-cell currents consistent with changes in TREK-1 activity. Responses were absent when particles were coated with RGD (Arg–Gly–Asp) peptide or when magnetic fields were applied in the absence of magnetic particles. It is concluded that changes in whole-cell current are the result of direct force application to the extracellular loop region of TREK-1 and thus these results implicate this region of the channel structure in mechano-gating. It is hypothesized that the extended loop region of TREK-1 may act as a tension spring that acts to regulate sensitivity to mechanical forces, in a nature similar to that described for MscL. The development of a technique that permits the direct manipulation of mechanosensitive ion channels in real time without the need for pharmacological drugs has huge potential benefits not only for basic biological research of ion-channel gating mechanisms, but also potentially as a tool for the treatment of human diseases caused by ion-channel dysfunction.

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Faculty Opinions recommendation of Mechanosensitive ion channels in cultured sensory neurons of neonatal rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1063865.516803 ◽

2007 ◽

Author(s):

Jaime García-Añoveros

Keyword(s):

Ion Channels ◽

Sensory Neurons ◽

Neonatal Rats ◽

Mechanosensitive Ion Channels

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Faculty Opinions recommendation of Modulation of cardiac mechanosensitive ion channels involves superoxide, nitric oxide and peroxynitrite.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1161664.628493 ◽

2009 ◽

Author(s):

John Jeremy Rice

Keyword(s):

Nitric Oxide ◽

Ion Channels ◽

Mechanosensitive Ion Channels

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The Use of Inhibitors of Mechanosensitive Ion Channels as Local Inhibitors of Peripheral Pain

10.21236/ada611580 ◽

2014 ◽

Cited By ~ 3

Author(s):

Frederick Sachs

Keyword(s):

Ion Channels ◽

Mechanosensitive Ion Channels ◽

Peripheral Pain

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Biophysics and Modeling of Mechanotransduction in Neurons: A Review

Mathematics ◽

10.3390/math9040323 ◽

2021 ◽

Vol 9 (4) ◽

pp. 323

Author(s):

Martina Nicoletti ◽

Letizia Chiodo ◽

Alessandro Loppini

Keyword(s):

Ion Channels ◽

Cell Membrane ◽

Sensory Neurons ◽

Neuronal Cell ◽

Molecular Processes ◽

Biological Mechanisms ◽

Mechanosensitive Ion Channels ◽

Complex Interactions ◽

Different Types ◽

Intracellular Organelles

Mechanosensing is a key feature through which organisms can receive inputs from the environment and convert them into specific functional and behavioral outputs. Mechanosensation occurs in many cells and tissues, regulating a plethora of molecular processes based on the distribution of forces and stresses both at the cell membrane and at the intracellular organelles levels, through complex interactions between cells’ microstructures, cytoskeleton, and extracellular matrix. Although several primary and secondary mechanisms have been shown to contribute to mechanosensation, a fundamental pathway in simple organisms and mammals involves the presence of specialized sensory neurons and the presence of different types of mechanosensitive ion channels on the neuronal cell membrane. In this contribution, we present a review of the main ion channels which have been proven to be significantly involved in mechanotransduction in neurons. Further, we discuss recent studies focused on the biological mechanisms and modeling of mechanosensitive ion channels’ gating, and on mechanotransduction modeling at different scales and levels of details.

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