Mammalian TRP ion channels are insensitive to membrane stretch

Abstract

TRP 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, it is unclear in many instances 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 subfamilies. We found that these TRP channels were insensitive to short membrane stretch 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 they are more likely activated by cytoplasmic tethers or downstream components and act as amplifiers of cellular mechanosensory signaling cascades.