Plasma Membrane Mechanical Stress Activates TRPC5 Channels

Abstract

Mechanical forces exerted on cells impose stress on the plasma membrane. Cells sense this stress and elicit a mechanoelectric transduction cascade that initiates compensatory mechanisms. Mechanosensitive ion channels in the plasma membrane are responsible for transducing the mechanical signals to electrical signals. However, the mechanisms underlying channel activation in response to mechanical stress remain incompletely understood. Transient Receptor Potential (TRP) channels serve essential functions in several sensory modalities. These channels can also participate in mechanotransduction by either being autonomously sensitive to mechanical perturbation or by coupling to other mechanosensory components of the cell. Here, we investigated the response of a TRP family member, TRPC5, to mechanical stress. Hypoosmolarity triggers Ca2+ influx and cationic conductance through TRPC5. Importantly, for the first time we were able to record the stretch-activated TRPC5 current at single-channel level. The activation threshold for TRPC5 was found to be 240 mOsm for hypoosmotic stress and between −20 and −40 mmHg for pressure applied to membrane patch. In addition, we found that disruption of actin filaments suppresses TRPC5 response to hypoosmotic stress and patch pipette pressure, but does not prevent the activation of TRPC5 by stretch-independent mechanisms, indicating that actin cytoskeleton is an essential transduction component that confers mechanosensitivity to TRPC5. In summary, our findings establish that TRPC5 can be activated at the single-channel level when mechanical stress on the cell reaches a certain threshold.

Mammalian TRP ion channels are insensitive to membrane stretch

“…As a control, we used the well-characterized mechanosensitive Piezo1 and MscL channels, which under the same experimental conditions exhibited robust stretch-activated ion currents in cell and liposome membrane patches, respectively. Overall, our results contrast with the results reported in many studies describing TRP channel activation by membrane stretching, which has been reported numerous times to activate TRP channels: TRPV4 (Loukin et al, 2010), TRPA1 (Kwan et al, 2006), PKD1/ PKD2 (TRPP2) (Nauli et al, 2003), TRPC1 (Maroto et al, 2005), TRPM4 (Morita et al, 2007), TRPC5 (Shen et al, 2015) and TRPC6 (Spassova et al, 2006;Wilson and Dryer, 2014;Anderson et al, 2013;Yamaguchi et al, 2017;Dyachenko et al, 2009). Notably, inherent mechanosensitivitywhich would suggest TRP channels to be primary mechanosensorswas never provided for any of these channels.…”

How a High-Gradient Magnetic Field Could Affect Cell Life

“…Additional membrane tension, in our case induced by the high-gradient magnetic field, can increase the probability of mechanosensitive channel opening44. Thus, plasma membrane mechanical stress activates transient receptor potential (TRP) channels45. Below, we calculate the mechanical forces and stress in a cell placed in an HGMF.…”

Redox regulation of transient receptor potential channels in the endothelium

“…Ca 2+ released from intracellular stores following the opening of inositol-triphosphate receptors or Ca 2+ influx through Ca 2+ -permeable ion channels located in the plasma membrane increase global or localized intracellular endothelial [Ca 2+ ] to stimulate Ca 2+ -dependent signaling pathways. Endothelial cells are non-excitable cells (i.e., lacking voltage-gated ion channels) and the activation of Ca 2+ -permeable channels occurs by chemical and physical stimuli, such as membrane stretch caused by intraluminal pressure and shear stress 4-6 , or by soluble substances produced by autocrine or paracrine mechanisms. This review is focused on the control of endothelial cell Ca 2+ influx by reduction-oxidation reactions (redox) regulation, defined here as reactions in which the oxidation states of atoms are changed.…”