title: Heart failure induces changes in acid-sensing ion channels in sensory neurons innervating skeletal muscle.
abstract: Heart failure is associated with diminished exercise capacity, which is driven, in part, by alterations in exercise-induced autonomic reflexes triggered by skeletal muscle sensory neurons (afferents). These overactive reflexes may also contribute to the chronic state of sympathetic excitation, which is a major contributor to the morbidity and mortality of heart failure. Acid-sensing ion channels (ASICs) are highly expressed in muscle afferents where they sense metabolic changes associated with ischaemia and exercise, and contribute to the metabolic component of these reflexes. Therefore, we tested if ASICs within muscle afferents are altered in heart failure. We used whole-cell patch clamp to study the electrophysiological properties of acid-evoked currents in isolated, labelled muscle afferent neurons from control and heart failure (induced by myocardial infarction) mice. We found that the percentage of muscle afferents that displayed ASIC-like currents, the current amplitudes, and the pH dose-response relationships were not altered in mice with heart failure. On the other hand, the biophysical properties of ASIC-like currents were significantly different in a subpopulation of cells (40%) from heart failure mice. This population displayed diminished pH sensitivity, altered desensitization kinetics, and very fast recovery from desensitization. These unique properties define these channels within this subpopulation of muscle afferents as being heteromeric channels composed of ASIC2a and -3 subunits. Heart failure induced a shift in the subunit composition of ASICs within muscle afferents, which significantly altered their pH sensing characteristics. These results might, in part, contribute to the changes in exercise-mediated reflexes that are associated with heart failure.
authors: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.|The Department of Veterans Medical Center, Iowa City, IA, 52242, USA.
authors: David D
authors: DD
authors: Gibbons
authors: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
authors: William J
authors: WJ
authors: Kutschke
authors: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
authors: Robert M
authors: RM
authors: Weiss
authors: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.|The Department of Veterans Medical Center, Iowa City, IA, 52242, USA.
authors: Christopher J
authors: CJ
authors: Benson
mesh_terms: D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000818:Animals; D005727:Ganglia, Spinal / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology*; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D010805:Physical Conditioning, Animal; D011984:Sensory Receptor Cells / Q000502:physiology*
chemical_list: D062565:Acid Sensing Ion Channels