Abstract
Murine slowly adapting receptors (SARs) within airway smooth muscle provide volume-related feedback; however, their mechanosensitivity and morphology are incompletely characterized. We explored two aspects of SAR physiology: their inherent static mechanosensitivity and a potential link to pulmonary neuroepithelial bodies (NEBs). SAR mechanosensitivity displays a rate sensitivity linked to speed of inflation; however, to what extent static SAR mechanosensitivity is tuned for the very rapid breathing frequency (B (f) ) of small mammals (e.g., mouse) is unclear. NEB-associated, morphologically described smooth muscle-associated receptors (SMARs) may be a structural analog for functionally characterized SARs, suggesting functional linkages between SARs and NEBs. We addressed the hypotheses that: (1) rapid murine B (f) is associated with enhanced in vivo SAR static sensitivity; (2) if SARs and NEBs are functionally linked, stimuli reported to impact NEB function would alter SAR mechanosensitivity. We measured SAR action potential discharge frequency (AP f, action potentials/s) during quasi-static inflation [0-20 cmH(2)O trans-respiratory pressure (P(TR))] in NEB-relevant conditions of hypoxia (F(I)O(2) = 0.1), hypercarbia (F(I)CO(2) = 0.1), and pharmacologic intervention (serotonergic 5-HT(3) receptor antagonist, Tropisetron, 4.5 mg/kg; P2 purinergic receptor antagonist, Suramin, 50 mg/kg). In all protocols, we obtained: (1) AP f vs. P(TR); (2) P(TR) threshold; and (3) AP f onset at P(TR) threshold. The murine AP f vs. P(TR) response comprises high AP f (average maximum AP f: 236.1 ± 11.1 AP/s at 20 cmH(2)O), a low P(TR) threshold (mean 2.0 ± 0.1 cmH(2)O), and a plateau in AP f between 15 and 20 cmH(2)O. Murine SAR mechanosensitivity (AP f vs. P(TR)) is up to 60% greater than that reported for larger mammals. Even the maximum difference between intervention and control conditions was minimally impacted by NEB-related alterations: Tropisetron -7.6 ± 1.8% (p = 0.005); Suramin -10.6 ± 1.5% (p = 0.01); hypoxia +9.3 ± 1.9% (p < 0.001); and hypercarbia -6.2 ± 0.9% (p < 0.001). We conclude that the high sensitivity of murine SARs to inflation provides enhanced resolution of operating lung volume, which is aligned with the rapid B (f) of the mouse. We found minimal evidence supporting a functional link between SARs and NEBs and speculate that the <10% change in SAR mechanosensitivity during altered NEB-related stimuli is not consistent with a meaningful physiologic role.