Structural Elements for the Generation of Sustained Currents by the Acid Pain Sensor ASIC3

摘要: ASIC3 is an acid-sensing ion channel expressed in sensory neurons, where it participates acidic and inflammatory pain. In addition to the "classical" transient current, generates a sustained current essential for pain perception. Using chimeras between ASIC1a channels we show that first transmembrane domain (TM1), combined with N-terminal domain, key structural element generating low pH (<6.5)-evoked current. The TM1 also modulates pH-dependent activation of fast thus contributing constitutive window another type present near physiological pH. C-terminal TM2 domains negatively regulate both types extracellular loop affects its kinetics. These data provide new information aid understanding mechanisms multifaceted gating ASIC3. Together peak components (window at <6.5) allow adapt behavior wide range variations by and/or responses contribute nociceptor excitability.