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

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.