Key role for the multimodal CaSR in pulmonary neuroepithelial body microenvironment physiology

The neuroepithelial body (NEB) microenvironment consists of densely innervated groups of neuroendocrine cells, representing complex sensory receptors in the airways, and a stem cell population. The extracellular Ca 2+ ‐sensing receptor (CaSR) is a master regulator of extracellular free ionized Ca 2+ ([Ca 2+ ] o ), and a multimodal sensor able to integrate inputs from a variety of physiological stimuli. Immunostaining and (q)RT‐PCR recently revealed a selective CaSR expression on the plasmamembrane of NEB cells in postnatal mouse lungs. We further aimed at exploring potential roles for the CaSR in pulmonary NEB physiology. Ca 2+ imaging of mouse lung slices demonstrated a CaSR‐mediated rise in intracellular Ca 2+ concentration ([Ca 2+ ] i ) following an increase of [Ca 2+ ] o or application of established CaSR agonists. The CaSR was shown to be involved in regulating baseline [Ca 2+ ] i in NEBs, and in mediating intercellular communication in the NEB microenvironment. By integrating multiple physio(patho)logical signals and coordinating intra‐ and extracellular Ca 2+ signaling, the CaSR appears to serve key roles for the NEB microenvironment as a complex chemosensory receptor and airway stem cell niche.