title: Muscarinic M1 modulation of acid-sensing ion channels.
abstract: Acid-sensing ion channels (ASICs) are ligand-gated cation channels that are highly expressed in nervous system. Little is known about the regulation of these channels. Therefore, we tested whether muscarinic M1 receptors can modulate ASICs. The muscarinic agonist oxotremorine methiodide applied to the bath solution strongly inhibited the whole-cell current in Chinese hamster ovary cells heterologously expressing ASIC1a and M1 receptors. Maximal current was inhibited 30% during muscarinic receptor stimulation. These effects were fast, fully reversible and subunit specific. The acid-sensing current in population of isolated rat hippocampus CA1 and striatum interneurons, thought to be carried primarily by ASIC1a, was similarly inhibited by oxotremorine methiodide. Thus, the current study identifies ASIC1a as a novel target for muscarinic signaling.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, 53226, USA.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Dorofeeva
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Karpushev
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Nikolaev
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Bolshakov
authors.forename: James D
authors.initials: JD
authors.lastname: Stockand
authors.forename: Alexander
authors.initials: A
authors.lastname: Staruschenko
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D016466:CHO Cells; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D010095:Oxotremorine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D062565:Acid Sensing Ion Channels; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D043643:Receptor, Muscarinic M1; D015222:Sodium Channels; D010095:Oxotremorine