ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1

摘要: ASIC3, an acid-sensing ion channel subunit expressed essentially in sensory neurons, has been proposed to be involved pain. We show here for the first time that native ASIC3-like currents were increased cultured dorsal root ganglion (DRG) neurons following protein kinase C (PKC) stimulation. This increase was induced by phorbol ester PDBu and pain mediators, such as serotonin, which are known activate PKC pathway through their binding G protein-coupled receptors. demonstrate this regulation involves silent ASIC2b subunit, ASIC also neurons. Indeed, heteromultimeric ASIC3/ASIC2b channels, but not homomeric ASIC3 positively regulated PKC. The of current is accompanied a shift its pH dependence toward more physiological values may lead neuron excitability. requires PICK-1 (protein interacting with kinase), PDZ domain-containing protein, interacts terminus.