ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac dorsal root ganglia neurons.

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.

• Authors: Tomonori Hattori, Jie Chen, Anne Marie S Harding, Margaret P Price, Yongjun Lu, Francois M Abboud, Christopher J Benson
• Journal: Circulation research (Circ Res) Vol. 105 Issue 3 Pg. 279-86 (Jul 31 2009) ISSN: 1524-4571 [Electronic] United States
• PMID: 19590043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ASIC2 protein, mouse
• ASIC3 protein, mouse
• Acid Sensing Ion Channels
• Nerve Tissue Proteins
• Protons
• Sodium Channels
• Adenosine Triphosphate
• Capsaicin

Topics

• Acid Sensing Ion Channels
• Adenosine Triphosphate (pharmacology)
• Animals
• Capsaicin (pharmacology)
• Cells, Cultured
• Ganglia, Spinal (cytology, drug effects, metabolism)
• Heart (innervation)
• Hydrogen-Ion Concentration
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nerve Tissue Proteins (genetics, metabolism)
• Neurons (cytology, metabolism)
• Patch-Clamp Techniques
• Protein Multimerization (physiology)
• Protons
• Sodium Channels (genetics, metabolism)