KCNK3 channel is important for the ventilatory response to hypoxia in rats

Céline-Hivda Yegen; Mélanie Lambert; Antoine Beurnier; David Montani; Marc Humbert; Carole Planès; Emilie Boncoeur; Nicolas Voituron; Fabrice Antigny

doi:10.1016/j.resp.2023.104164

KCNK3 channel is important for the ventilatory response to hypoxia in rats

Respir Physiol Neurobiol. 2023 Dec:318:104164. doi: 10.1016/j.resp.2023.104164. Epub 2023 Sep 20.

Authors

Céline-Hivda Yegen¹, Mélanie Lambert², Antoine Beurnier³, David Montani⁴, Marc Humbert⁴, Carole Planès⁵, Emilie Boncoeur¹, Nicolas Voituron⁶, Fabrice Antigny⁷

Affiliations

¹ Laboratoire Hypoxie & Poumon, UMR INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France.
² Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.
³ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM UMR_S 999 " Hypertension pulmonaire: Physiopathologie et Innovation Thérapeutique ", Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Service de Physiologie et d'explorations fonctionnelles, Hôpital Avicenne, APHP, Hôpitaux de Paris, France.
⁴ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM UMR_S 999 " Hypertension pulmonaire: Physiopathologie et Innovation Thérapeutique ", Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
⁵ Laboratoire Hypoxie & Poumon, UMR INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France; AP-HP, Department of Physiology - Functional Explorations, DMU Thorinno, bi-site Hôpital Bicêtre (Le Kremlin Bicêtre) and Ambroise Paré (Boulogne-Billancourt), France.
⁶ Laboratoire Hypoxie & Poumon, UMR INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France; Département STAPS, Université Sorbonne Paris Nord, Bobigny, France. Electronic address: nicolas.voituron@sorbonne-paris-nord.fr.
⁷ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France. Electronic address: fabrice.antigny@inserm.fr.

PMID: 37739151
DOI: 10.1016/j.resp.2023.104164

Abstract

To clarify the contribution of KCNK3/TASK-1 channel chemoreflex in response to hypoxia and hypercapnia, we used a unique Kcnk3-deficient rat. We assessed ventilatory variables using plethysmography in Kcnk3-deficient and wild-type rats at rest in response to hypoxia (10% O₂) and hypercapnia (4% CO₂). Immunostaining for C-Fos, a marker of neuronal activity, was performed to identify the regions of the respiratory neuronal network involved in the observed response.Under basal conditions, we observed increased minute ventilation in Kcnk3-deficient rats, which was associated with increased c-Fos positive cells in the ventrolateral region of the medulla oblongata. Kcnk3-deficient rats show an increase in ventilatory response to hypoxia without changes in response to hypercapnia. In Kcnk3-deficient rats, linked to an increased hypoxia response, we observed a greater increase in c-Fos-positive cells in the first central relay of peripheral chemoreceptors and Raphe Obscurus. This study reports that KCNK3/TASK-1 deficiency in rats induces an inadequate peripheral chemoreflex, alternating respiratory rhythmogenesis, and hypoxic chemoreflex.

Keywords: Hypercapnia; Hypoxia; K2P3.1; Raphe obscurus; c-Fos.