Transient upregulation of TASK‐1 expression in the hypoglossal nucleus during chronic intermittent hypoxia is reduced by serotonin 2A receptor antagonist

Abstract

Hypoglossal motoneurons innervate genioglossus muscle, the contraction of which is critical in the maintenance of upper airway patency in patients with obstructive sleep apnea. As a potassium channel distributed in hypoglossal motoneurons, TWIK‐related acid‐sensitive K+ channel‐1 (TASK‐1) could be inhibited by 5‐HT. This study aimed to investigate if TASK‐1 expression in hypoglossal nucleus could be influenced by chronic intermittent hypoxia (CIH) and 5‐HT2A receptors antagonist. Two hundred twenty‐eight rats were exposed to CIH or normoxia (NO) in the presence and absence of 5‐HT 2A receptor antagonist (MDL‐100907) microinjected into the hypoglossal nucleus. The expression of 5‐HT and TASK‐1 in the hypoglossal nucleus were detected by immunohistochemistry and reverse transcription quantitative polymerase chain reaction on the 1st, 3rd, 7th, 14th and 21st day of CIH exposure. The mean optical density (MOD) of 5‐HT in the XII nucleus was significantly increased in the CIH and CIH + MDL group than the NO group on the 7th and 21st day ( p < 0.05). Compared with the NO group, the MOD and gene expression of TASK‐1 in the CIH group was significantly increased on the 7th and 14th day ( p < 0.05), then normalized on the 21st day. The TASK‐1 expression in the CIH + MDL group was significantly lower than the CIH + PBS and CIH group on the 7th and 14th day ( p < 0.05). The CIH‐induced transiently upregulation of the TASK‐1 expression in the hypoglossal nucleus could be reversed by 5‐HT 2A receptor antagonist, indicating that the modulation of the TASK‐1 expression in response to CIH involves 5‐HT and 5‐HT 2A receptors, and this CIH effect might be 5‐HT 2A receptor‐dependent.

Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones

“…These changes could also be mediated by the inhibitory effects of 5-HT and NA on TASK channels since noradrenergic and serotoninergic terminal density was increased in the HMN of rats submitted to CIH (Rukhadze et al 2010). On the other side, it was previously demonstrated that CIH increases TASK-1 protein expression in the HMN of rats, despite not identifying which type of hypoglossal motoneurones was affected (Li et al 2019). Therefore, additional experiments are needed to evaluate the expression of TASK-1 and TASK-3 in the protrudor and retractor hypoglossal motoneurones from rats submitted to CIH.…”

“…On the other side, it was previously demonstrated that CIH increases TASK‐1 protein expression in the HMN of rats, despite not identifying which type of hypoglossal motoneurones was affected (Li et al . 2019). Therefore, additional experiments are needed to evaluate the expression of TASK‐1 and TASK‐3 in the protrudor and retractor hypoglossal motoneurones from rats submitted to CIH.…”

“…2020), serotonin density and TASK‐1 expression in the HMN (Li et al . 2019), as well as on the ultrastructure of the genioglossus muscle (Meng et al . 2020) were similar between the 7th and 10th day of exposure.…”

Role of Raphe Magnus 5-HT1A Receptor in Increased Ventilatory Responses Induced by Intermittent Hypoxia in Rats

“…The coordinates of RMg were 10.52-11.30 mm from the bregma in the midline and 10.4 mm below the dorsal surface of the skull according to the Paxinos and Watson atlas [22]. The procedure for guide cannula and the matched injection cannula implantation into the RMg region was described in previous studies [23].…”

Defective X-gating caused byde novogain-of-function mutations inKCNK3underlies a developmental disorder with sleep apnea

“…In peripheral tissues, TASK-1 is also found in the carotid bodies, lung, heart, and pulmonary arterial smooth muscle [15][16][17] . Its expression throughout these tissues has therefore implicated TASK-1 in the control of breathing and also in sleep apnea 12,[18][19][20][21][22] . Furthermore, an X-ray crystal structure of the TASK-1 channel has recently been reported in complex with a compound class of TASK-1 inhibitors currently in clinical trials for the treatment of sleep apnea 23 .…”