Oral Presentation 2014 International Biophysics Congress

Neurosensory mechanotransduction through acid-sensing ion channels (#96)

Chih-Cheng Chen 1 , Shing-Hong Lin 1 , Wei-Hsin Sun 2 , Yuan-Ren Cheng 3
  1. Academia Sinica, Taipei, Taiwan
  2. Life Sciences, National Central University, Jhongli, Taiwan
  3. Life Sciences, National Taiwan University, Taipei, Taiwan

Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive, proton-gated ion channels that belong to the degenerin/epithelial sodium channel family of ion channels. In mammals, the ASIC family consists of at least 7 isoforms—ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, and ASIC5—encoded by 5 genes (Accn1-5). Though ASICs are involved in acid signaling throughout the peripheral and central nervous systems, however, their possible roles in mechano-sensing are disputed. Based on genetic ablation (gene knockout) studies, mice lacking an ASIC isoform showed different deficits in neurosensory mechanotransduction in physiological and behavioral responses to mechanical stimuli. Nevertheless, studies on dissociated sensory neurons did not support a role for ASICs in mechanotransduction. Moreover, electrical recordings on sensory nerve showed either enhanced or reduced mechanotransduction in tissues isolated from ASIC1, ASIC2, or ASIC3 knockout mice. We reasoned previous ASIC knockout studies failed to address the heterogeneous expression of ASICs in sensory neuron subtypes and did not use a proper electrophysiological approach in vitro to probe the role of ASICs in mechanotransduction in a physiologically relevant condition. We report here a genetic axonal tracing approach to probe ASIC function in a small and homogeneous population of parvalbumin-positive sensory neurons. Conditional knockout of ASIC in these neurons not only greatly attenuates acid sensing but also eliminates a specific mechanosensing response in these neurons. The physiological importance of ASIC in these parvalbumin-positive neurons is further supported by deficits in proprioceptive behavior in tests on the conditional ASIC knockout mice.