ASIC2 and 3 contribute to the composition of ASICs in murine sympathetic cardiac afferents

Acid‐Sensing Ion Channels (ASICs) are proton‐gated channels that are highly expressed in cardiac afferents. 4 genes encode ASICs; our objective here was to determine the subunit composition in cardiac afferents. Whole‐cell patch‐clamp experiments were performed on cultured upper thoracic (C8‐T3) dorsal root ganglia (DRG) neurons from wild type (WT) or ASIC knockout (KO) mice. To identify cardiac afferents, we injected a retrograde tracer dye into the pericardial cavity 3 weeks prior to culturing DRG neurons. Both labeled cardiac neurons (CNs) and unlabeled non‐cardiac neurons (NCNs) from WT mice showed inward transient and sustained currents induced by acidic pH (4.0–7.0). The sustained currents in CNs were significantly larger than NCNs; whereas pH sensitivity, the time constants of desensitization at pH 5.0–7.0, and the recovery kinetics from desensitization were not different. Next, we studied the CNs and NCNs from ASIC3 KO mice; both still showed pH‐activated currents, however CNs were less pH sensitive than NCNs. The pH sensitivity of CNs from ASIC3 KO mice matched that of ASIC2 homomultimeric channels. These results suggest that ASICs in cardiac DRG afferents are likely composed of ASIC2/3 heteromultimers. To confirm our findings, we are investigating DRG neurons from ASIC2 KO and ASIC 2/3 double KO mice. Supported by NIH.