Pulmonary neuroendocrine H146 cells as hypercapnic sensors

Abstract

Singular pulmonary neuroendocrine cells (pNEC) or clusters called pulmonary neuroepithelial bodies (NEBs) are widely distributed within the airway mucosa of human and mammalian lungs. NEB cells produce amines (e.g. 5‐HT), and are thought to modulate the control of breathing in response to low O2 conditions (hypoxia). The mechanism by which these cells detect hypoxia is thought to occur via activity of NADPH oxidase in conjunction with K+ channels. Exposure of NEBs to hypoxia causes K+ channel closure, membrane depolarization and 5‐HT release. In other chemosensory organs (e.g. the well studied carotid body) the sensory cells are often polymodal, capable of responding to high CO2 levels (hypercapnia) and/or hypoxia (usually via different mechanisms). However it is currently unknown whether NEBs can sense hypercapnia in addition to hypoxia. Using molecular biology, immunocytochemistry, and electrophysiology we explore whether H146 cells (a model cell line of pNEC/NEB) are capable of responding hypercapnia. In other hypercapnic sensing organs (e.g. adrenal chromaffin cells), carbonic anhydrase 2 (CA II) is thought to play a role in mediating the hypercapnic response. Although native NEB do express this isoform (among several others), CA II is not expressed in H146 cells. Nevertheless they do respond to hypercapnia via membrane depolarization and 5‐HT release, as determined using electrophysiology. This finding suggests that another isoform of CA or alternate mechanism may be involved in mediating hypercapnic sensitivity in H146 cells. Funded by: NSERC Discovery Grant