title: Acid sensing ion channels regulate neuronal excitability by inhibiting BK potassium channels.
abstract: Acid sensing ion channels (ASICs), Ca(2+) and voltage-activated potassium channels (BK) are widely present throughout the central nervous system. Previous studies have shown that when expressed together in heterologous cells, ASICs inhibit BK channels, and this inhibition is relieved by acidic extracellular pH. We hypothesized that ASIC and BK channels might interact in neurons, and that ASICs may regulate BK channel activity. We found that ASICs inhibited BK currents in cultured wild-type cortical neurons, but not in ASIC1a/2/3 triple knockout neurons. The inhibition in the wild-type was partially relieved by a drop in extracellular pH to 6. To test the consequences of ASIC-BK interaction for neuronal excitability, we compared action potential firing in cultured cortical neurons from wild-type and ASIC1a/2/3 null mice. We found that in the knockout, action potentials were narrow and exhibited increased after-hyperpolarization. Moreover, the excitability of these neurons was significantly increased. These findings are consistent with increased BK channel activity in the neurons from ASIC1a/2/3 null mice. Our data suggest that ASICs can act as endogenous pH-dependent inhibitors of BK channels, and thereby can reduce neuronal excitability.
authors.affiliation: Department of Biology and Molecular Biology, Montclair State University, Montclair, NJ 07043, USA. petroffe@mail.montlcair.edu
authors.forename: Elena
authors.initials: E
authors.lastname: Petroff
authors.forename: Vladislav
authors.initials: V
authors.lastname: Snitsarev
authors.forename: Huiyu
authors.initials: H
authors.lastname: Gong
authors.forename: Francois M
authors.initials: FM
authors.lastname: Abboud
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels