Genetic exploration of roles of acid-sensing ion channel subtypes in neurosensory mechanotransduction including proprioception.

Although acid-sensing ion channels (ASICs) are proton-gated ion channels responsible for sensing tissue acidosis, accumulating evidence has shown that ASICs are also involved in neurosensory mechanotransduction. However, in contrast to Piezo ion channels, evidence of ASICs as mechanically gated ion channels has not been found using conventional mechanoclamp approaches. Instead, ASICs are involved in the tether model of mechanotransduction, with the channels gated via tethering elements of extracellular matrix and intracellular cytoskeletons. Methods using substrate deformation-driven neurite stretch and micropipette-guided ultrasound were developed to reveal the roles of ASIC3 and ASIC1a, respectively. Here we summarize the evidence supporting the roles of ASICs in neurosensory mechanotransduction in knockout mouse models of ASIC subtypes and provide insight to further probe their roles in proprioception. NEW FINDINGS: What is the topic of this review? The roles of acid-sensing ion channels in mechanotransduction, including proprioception, along with new investigative approaches. What advances does it highlight? New methods such as substrate deformation-driven neurite stretch and micropipette-guided ultrasound can help in studying the functions and electrophysiological properties of ASICs essential for a tether model of mechanotransduction, especially conduction of proprioceptive signals from the muscle spindle to specific groups of dorsal root ganglion neurons.