Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b

Acid-sensing ion channels (ASICs) are activated by extracellular protons an d are involved in neurotransmission in the central nervous system, in pain perception, as well as in mechanotransduction. Six different ASIC subunits have been cloned to date, which are encoded by four genes (ASIC1-ASIC4). Pr oton-gated currents have been described in isolated neurons from sensory ga nglia as well as from central nervous system. However, it is largely unclea r which of the cloned ASIC subunits underlie these native proton-gated curr ents. Recently, a splice variant, ASIC-beta, has been described for ASIC1a. In this variant about one-third of the protein is exchanged at the N termi nus. Here we show that ASIC-beta has a longer N terminus than previously re ported, extending the sequence divergence between ASIC1a and this new varia nt (ASIC1b). We investigated in detail kinetic and selectivity properties o f ASIC1b in comparison to ASIC1a. Kinetics is similar for ASIC1b and ASIC1a . Ca2+ permeability of ASIC1a is low, whereas ASIC1b is impermeable to Ca2. Currents through ASIC1a resemble currents, which have been described in s ensory and central neurons, whereas the significance of ASIC1b remains to b e established. Moreover, we show that a pre-transmembrane I domain controls the permeability to divalent cations in ASIC1, contributing to our underst anding of the pore structure of these channels.