ASIC1a channels in the locus coeruleus mediate hypercapnic acidosis detection and CO₂-induced panic behavior

There is a connection between respiratory pathologies and panic disorder, since episodes of hypercapnia can trigger anxiety-related behaviors. The locus coeruleus (LC) is a CO₂/pH chemosensitive region capable of generating emotional and physical responses during stress episodes. The acid-sensitive ion channel type 1a (ASIC1a) participates in the panicogenic response induced by CO₂.

Our study investigated the role of ASIC1a channels in the LC in detecting hypercapnic acidosis and their participation in the respiratory and behavioral responses induced by CO₂.

We tested the effects of injection of an ASIC1a antagonist [Psalmotoxin-1 (Pstx-1-50 ng/0.1uL)] into the LC of C57BL/6 male and female mice on respiratory, metabolic, and behavioral responses to 20% CO₂. To assess the role of ASIC1a channels in basal activity and CO₂ chemosensitivity of LC neurons, whole-cell patch-clamp recordings were performed on brainstem slices from male mice using Pstx-1 (0.050 µg/mL).

Pstx-1 intra-LC did not change ventilation and metabolism under normocapnic and hypercapnic conditions in both male and female mice. As to CO₂-behavioral responses, Pstx-1 injection decreased the number of jumps in males, but there was no significant difference in females. In vitro, Pstx-1 reduced the activity of LC chemoreceptors under hypercapnia in males, but no change was observed under control conditions.

ASIC1a channels in the LC do not participate in respiratory control under normocapnia and hypercapnia, but are involved in CO₂-induced panic behavior, demonstrating a sex-dependent response. Furthermore, ASIC1a channels contribute to the CO₂ chemosensitivity of LC neurons in males.