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

Carotid body (CB) glomus cells depolarize in response to hypoxia, causing a [Ca 2+ ] i increase through activation of voltage‐dependent Ca 2+ channels, resulting in neurotransmitter release and carotid sinus nerve excitation. Glomus cell mitochondria are believed to be the site of O 2 sensing. Previous work showed that perinatal chronic hypoxia (12% O 2 ) during CB postnatal maturation severely impairs CB glomus cell oxygen sensitivity. It is unknown whether chronic hypoxia (CH) impairs glomus cell mitochondrial O 2 sensing vs. downstream elements in the O 2 transduction cascade. We therefore studied the effects of CH on [Ca 2+ ] i and mitochondrial membrane potential (Δψ m ) in response to acute hypoxia, in CB glomus cells from rats exposed to hypoxia (10% O 2 ) 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 [Ca 2+ ] 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 Δψ m ; 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 [Ca 2+ ] i in response to acute hypoxia by a mechanism downstream of mitochondria. (Supported by Arkansas Biosciences Institute funds)