Journal article
ASIC2a and ASIC3 Heteromultimerize to Form pH-Sensitive Channels in Mouse Cardiac Dorsal Root Ganglia Neurons
Circulation research, Vol.105(3), pp.279-286
2009
DOI: 10.1161/CIRCRESAHA.109.202036
PMID: 19590043
Abstract
Rationale: Acid-sensing ion channels (ASICs) are Na+ channels that are activated by acidic pH. Their expression in cardiac afferents and remarkable sensitivity to small pH changes has made them leading candidates to sense cardiac ischemia.
Objective: Four genes encode six different ASIC subunits, however it is not yet clear which of the ASIC subunits contribute to the composition of ASICs in cardiac afferents.
Methods and Results: Here, we labeled cardiac afferents using a retrograde tracer dye in mice, which allowed for patch-clamp studies of murine cardiac afferents. We found that a higher percentage of cardiac sensory neurons from the dorsal root ganglia respond to acidic pH and generated larger currents compared to those from the nodose ganglia. The ASIC-like current properties of the cardiac dorsal root ganglia neurons from wild-type mice most closely matched the properties of ASIC2a/3 heteromeric channels. This was supported by studies in ASIC-null mice: acid-evoked currents from ASIC3−/− cardiac afferents matched the properties of ASIC2a channels, and currents from ASIC2−/− cardiac afferents matched the properties of ASIC3 channels.
Conclusions: We conclude that ASIC2a and -3 are the major ASIC subunits in cardiac dorsal root ganglia neurons and provide potential molecular targets to attenuate chest pain and deleterious reflexes associated with cardiac disease.
Details
- Title: Subtitle
- ASIC2a and ASIC3 Heteromultimerize to Form pH-Sensitive Channels in Mouse Cardiac Dorsal Root Ganglia Neurons
- Creators
- Tomonori HATTORI - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesJie Chen - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesAnne Marie S HARDING - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesMargaret P PRICE - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesYongjun Lu - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesFrancois M ABBOUD - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United StatesChristopher J BENSON - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.105(3), pp.279-286
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1161/CIRCRESAHA.109.202036
- PMID
- 19590043
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 2009
- Academic Unit
- Molecular Physiology and Biophysics; Critical Care; Stead Family Department of Pediatrics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984025477202771
Metrics
17 Record Views