Pickpocket1 is a Drosophila Acid‐Sensing Na+ Channel Necessary for Proprioception

Abstract

The role of acid‐sensing channels during the normal function of the nervous system is poorly defined. Pickpocket1, PPK1, is a DEG/ENaC homolog restrictively expressed in Drosophila class IV multidentritic (md) sensory neurons. These channels are believed to be involved in sensory proprioception, but an exact mechanism is undefined. Using a primary neuronal culture from Drosophila embryos and whole cell patch‐clamping, we identify amiloride‐sensitive sustained (Is) and transient (It) acid‐sensing Na+ currents in md neurons. The robust sustained pH‐sensitive current is Na+ and K+‐selective and sensitive to amiloride but refractory to ruthenium red. A distinct transient sodium current is revealed by relief from inhibition following extracellular acidification. This transient pH‐sensitive current is absent in ppk1 −/− flies and rescued by targeted expression of a PPK1‐transgene identifying it as the PPK1 current. PPK1 function in md sensory neurons is necessary for normal Drosophila larvae proprioception consistent with PPK1 functioning as a molecular mechanosensory transducer. PPK1 activity is not required for intrinsic excitability but rather transduces dynamic sensory input essential to proprioception.