title: Subunit-specific inhibition of acid sensing ion channels by stomatin-like protein 1.
abstract: There are five mammalian stomatin-domain genes, all of which encode peripheral membrane proteins that can modulate ion channel function. Here we examined the ability of stomatin-like protein 1 (STOML1) to modulate the proton-sensitive members of the acid-sensing ion channel (ASIC) family. STOML1 profoundly inhibits ASIC1a, but has no effect on the splice variant ASIC1b. The inactivation time constant of ASIC3 is also accelerated by STOML1. We examined STOML1 null mutant mice with a β-galactosidase-neomycin cassette gene-trap reporter driven from the STOML1 gene locus, which indicated that STOML1 is expressed in at least 50% of dorsal root ganglion (DRG) neurones. Patch clamp recordings from mouse DRG neurones identified a trend for larger proton-gated currents in neurones lacking STOML1, which was due to a contribution of effects upon both transient and sustained currents, at different pH, a finding consistent with an endogenous inhibitory function for STOML1.
authors.affiliation: Department of Neuroscience, Growth Factor & Regeneration Group, Max-Delbrueck Center for Molecular Medicine, Robert-Roessle Strasse 10, D-13092 Berlin, Germany. es336@cam.ac.uk or glewin@mdc-berlin.de.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kozlenkov
authors.forename: Liudmila
authors.initials: L
authors.lastname: Lapatsina
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
authors.forename: Ewan St John
authors.initials: ES
authors.lastname: Smith
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000200:Action Potentials; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005727:Ganglia, Spinal / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism
chemical_list: C568267:ASIC1 protein, mouse; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C000592429:STOML1 protein, mouse