Abstract
ABSTRACTTRP channels of the transient receptor potential ion channel superfamily are involved in a wide variety of mechanosensory processes, including touch sensation, pain, blood pressure regulation, bone loading and detection of cerebrospinal fluid flow. However, in many instances it is unclear whether TRP channels are the primary transducers of mechanical force in these processes. In this study, we tested stretch activation of eleven TRP channels from six mammalian subfamilies. We found that these TRP channels were insensitive to short membrane stretches in cellular systems. Furthermore, we purified TRPC6 and demonstrated its insensitivity to stretch in liposomes, an artificial bilayer system free from cellular components. Additionally, we demonstrated that, when expressed in C. elegans neurons, mouse TRPC6 restores the mechanoresponse of a touch insensitive mutant but requires diacylglycerol for activation. These results strongly suggest that the mammalian members of the TRP ion channel family are insensitive to tension induced by cell membrane stretching and, thus, are more likely to be activated by cytoplasmic tethers or downstream components and to act as amplifiers of cellular mechanosensory signaling cascades.
Highlights
Transient receptor potential (TRP) ion channels constitute a superfamily of non-selective cationic channels permeable to Na+, Ca2+ and Mg2+, comprising 33 members found in mammals, of which 27 are found in humans (Clapham, 2003; Martinac and Cox, 2017)
TRP channels expressed in heterologous systems are insensitive to membrane stretch Given the important role that TRP channels play in mechanosensory processes, we sought to determine whether these ion channels are sensitive to membrane stretch
We recorded the activity of TRPC family members TRPC3, TRPC5 and TRPC6 in response to negative pressure pulses that had been applied to cell-attached patches for 300 ms (Fig. 1B–D)
Summary
Transient receptor potential (TRP) ion channels constitute a superfamily of non-selective cationic channels permeable to Na+, Ca2+ and Mg2+, comprising 33 members found in mammals, of which 27 are found in humans (Clapham, 2003; Martinac and Cox, 2017). Multiple studies have demonstrated TRP channel involvement in mechanosensory transduction in mammals (Spassova et al, 2006; Wilson and Dryer, 2014; Spassova et al, 2004; Welsh et al, 2002; Quick et al, 2012), including most notably TRPA1 (Corey et al, 2004), TRPV4 (Loukin et al, 2010), TRPV2 (Muraki et al, 2003; Katanosaka et al, 2014), PKD2 (Narayanan et al, 2013), PKD2L1 (Sternberg et al, 2018), TRPC3 and TRPC6 (Nikolova-Krstevski et al, 2017; Quick et al, 2012; Seo et al, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
