CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCEMuscarinic M1 modulation of acid-sensing ion channelsDorofeeva, Natalia A.c; Karpushev, Alexey V.a; Nikolaev, Maxim V.c; Bolshakov, Konstantin V.c; Stockand, James D.b; Staruschenko, AlexanderaAuthor Information aDepartment of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin bDepartment of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA cSechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia Correspondence to Dr Alexander Staruschenko, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA Tel: +1 414 456 8475; fax: +1 414 456 6546; e-mail: firstname.lastname@example.org Received 30 July 2009 accepted 4 August 2009 NeuroReport: October 7th, 2009 - Volume 20 - Issue 15 - p 1386-1391 doi: 10.1097/WNR.0b013e3283318912 Buy Metrics 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. © 2009 Lippincott Williams & Wilkins, Inc.