Murine Pulmonary Slowly‐Adapting Receptors (SARs): Putative links to Neuroepithelial Body (NEB) hypoxia chemoreception and the Calcium Sensing Receptor (CaSR)

Abstract

Pulmonary SARs are mechanosensitive vagal afferents, which Adriaensen (J Appl Physiol, 2006) proposed to be functionally linked to morphologically‐defined, hypoxia‐sensitive NEBs (Youngson et al. 1993, Nature). Post‐natal NEBs express CaSR (Lembrechts et al. 2013, J Cell Sci), and vagal NEB innervation expresses P2X2 and P2X3 ATP receptors (Brouns et al. 2009, Histochem Cell Biol). We tested in vivo murine SAR responses to quasi‐static inflation (0‐20 cmH2O) in: 1) hypoxia (10% O2) 2) absence of CaSR (CaSR / parathyroid hormone double‐knockout mouse, KO) and 3) P2 purinergic receptor blockade (Suramin: 50 mg/kg). SAR mechanosensitivity was defined as action potential frequency (f) at tracheal pressures of 5, 10, 15, and 20 cmH2O. Hypoxia caused a small but statistically significant increase in f (9.6±2.8% at 20cmH2O; P = 0.002, mean±SEM). Loss of CaSR significantly reduced f at all pressures (‐34.9% and ‐39.5% at 15cmH2O in hyper‐ and hypoxia, respectively; P < 0.001) with no impact of hypoxia within each genotype. Suramin caused a small but significant reduction in f (‐10.6±1.5% at 20cmH2O; P = 0.01). These data suggest that CaSR significantly impacts SAR mechanosensitivity, while purinergic signaling and hypoxia exert modest effects with as yet to be determined physiologic roles.Supported by CIHR MOP81211 (JTF), Spear Endowment for Respiratory Research (Queen's University JTF and RJM), NSERC PostGrad Scholarship (NJD).