Neuroepithelial bodies as airway hypoxia sensors: re‐evaluation of the concept in different mouse live cell imaging models (869.6)

Abstract

In pulmonary neuroepithelial bodies (NEBs), acute hypoxia has been suggested to close O2‐sensitive K+ channels, resulting in membrane depolarization, voltage‐gated Ca2+ entry and subsequent transmitter release.To visualize this mechanism in NEBs, our established live cell imaging (LCI) model, based on lung vibratome slices, was applied. Real‐time changes in different cellular processes were monitored during hypoxic challenge in NEBs of postnatal, prenatal and GAD67‐GFP mice.As a proof of concept, LCI experiments were performed on isolated mouse carotid body, proving that our LCI set up is indeed capable of visualizing hypoxia‐induced changes. However, in none of the NEBs studied in the lung slice models, severe (2% O2), mild (12% O2) or intermittent hypoxia, resulted in a rise in intracellular Ca2+ ([Ca2+]i) or subsequent neurotransmitter release. Moreover, low O2 levels appeared to decrease NEB cell excitability. The observed hypoxic mitochondrial membrane depolarization and increased ROS production rather seemed to be part of a general cellular defense mechanism, as supported by the non‐selective and non‐functional expression of the key O2 sensing protein NADPH oxidase.All together, our data argue for a reconsideration of the proposed straightforward hypoxic signal transduction pathway in pulmonary NEBs.Grants: FWO (G.0589.11), Hercules Foundation (AUAH‐09‐001); UA (GOA BOF 2007)