Psychopharmacology · 2025
ASIC1a channels in the locus coeruleus mediate hypercapnic acidosis detection and CO2-induced panic behavior.
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Pinheiro Letícia R, Frias Alana T, Patrone Luis Gustavo A, Bícego Kênia C, Zangrossi Hélio, Gargaglioni Luciane H
Аннотация
RATIONALE: 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.
OBJECTIVES: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVES: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.