| First Author | Hattori T | Year | 2009 |
| Journal | Circ Res | Volume | 105 |
| Issue | 3 | Pages | 279-86 |
| PubMed ID | 19590043 | Mgi Jnum | J:164935 |
| Mgi Id | MGI:4835641 | Doi | 10.1161/CIRCRESAHA.109.202036 |
| Citation | Hattori T, et al. (2009) ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac dorsal root ganglia neurons. Circ Res 105(3):279-86 |
| abstractText | 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. |
