title: Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
abstract: Acid-sensing ion channels (ASICs) are activated by extracellular protons and 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). Proton-gated currents have been described in isolated neurons from sensory ganglia as well as from central nervous system. However, it is largely unclear which of the cloned ASIC subunits underlie these native proton-gated currents. 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 terminus. Here we show that ASIC-beta has a longer N terminus than previously reported, extending the sequence divergence between ASIC1a and this new variant (ASIC1b). We investigated in detail kinetic and selectivity properties of ASIC1b in comparison to ASIC1a. Kinetics is similar for ASIC1b and ASIC1a. Ca(2+) permeability of ASIC1a is low, whereas ASIC1b is impermeable to Ca(2+). Currents through ASIC1a resemble currents, which have been described in sensory and central neurons, whereas the significance of ASIC1b remains to be established. Moreover, we show that a pre-transmembrane 1 domain controls the permeability to divalent cations in ASIC1, contributing to our understanding of the pore structure of these channels.
authors.affiliation: Department of Otolaryngology, Research Group of Sensory Physiology, Röntgenweg 11, D-72076 Tübingen, Germany.
authors.forename: E L
authors.initials: EL
authors.lastname: Bässler
authors.forename: T J
authors.initials: TJ
authors.lastname: Ngo-Anh
authors.forename: H S
authors.initials: HS
authors.lastname: Geisler
authors.forename: J P
authors.initials: JP
authors.lastname: Ruppersberg
authors.forename: S
authors.initials: S
authors.lastname: Gründer
mesh_terms: D062565:Acid Sensing Ion Channels; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D007477:Ions; D007700:Kinetics; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: C568266:ASIC1 protein, human; C112231:ASIC3 protein, human; C568270:ASIC4 protein, human; D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D018076:DNA, Complementary; D007477:Ions; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels; D002118:Calcium