Effect of Chronic Hypoxia on the Carotid Body Glomus Cell Mitochondrial Response to Acute Hypoxia

Abstract

Carotid body (CB) glomus cells depolarize in response to hypoxia, causing a [Ca2+]i increase through activation of voltage‐dependent Ca2+ channels, resulting in neurotransmitter release and carotid sinus nerve excitation. Glomus cell mitochondria are believed to be the site of O2 sensing. Previous work showed that perinatal chronic hypoxia (12% O2) during CB postnatal maturation severely impairs CB glomus cell oxygen sensitivity. It is unknown whether chronic hypoxia (CH) impairs glomus cell mitochondrial O2 sensing vs. downstream elements in the O2 transduction cascade. We therefore studied the effects of CH on [Ca2+]i and mitochondrial membrane potential (Δψm) in response to acute hypoxia, in CB glomus cells from rats exposed to hypoxia (10% O2) for 9‐14 days, starting at postnatal day 16‐18 (OxyCycler). Results show that 1) chronic hypoxia severely reduced glomus cell oxygen responsiveness to acute hypoxia as reflected by [Ca2+]i in ~80% of glomus cells; 2) chronic hypoxia did not affect the glomus cell response to 20mM KCl (a non‐specific depolarizing stimulus); 3) chronic hypoxia did not affect Δψm; 4) The reduced glomus cell oxygen sensitivity recovered after CH exposed rats were returned to room air. These results suggest that CH reversibly impairs glomus cell [Ca2+]i in response to acute hypoxia by a mechanism downstream of mitochondria. (Supported by Arkansas Biosciences Institute funds)