Calcium sensing receptor in developing human airway smooth muscle

Anne M. Roesler, Sarah A. Wicher, Jovanka Ravix, Rodney Jr. Britt, Logan Manlove, Jacob J. Teske, Katelyn Cummings, Michael A. Thompson, Carol Farver, Peter MacFarlane, Christina M Pabelick, Y.s. Prakash

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca2+ environment that may impact extracellular Ca2+ ([Ca2+]o) sensing receptor (CaSR). Well-known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18-22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca2+ ([Ca2+]i) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca2+ imaging showed that [Ca2+]i was more sensitive to altered [Ca2+]o. The fASM [Ca2+]i responses to histamine were also more sensitive to [Ca2+]o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca2+]i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5-triphosphate receptor (Xestospongin C) blunted [Ca2+]o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store-operated Ca2+ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca2+]o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca2+]o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - Jan 1 2019

    Fingerprint

Keywords

  • calcium
  • class C GPCR
  • contraction
  • fetal
  • lung
  • proliferation

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Roesler, A. M., Wicher, S. A., Ravix, J., Britt, R. J., Manlove, L., Teske, J. J., Cummings, K., Thompson, M. A., Farver, C., MacFarlane, P., Pabelick, C. M., & Prakash, Y. S. (Accepted/In press). Calcium sensing receptor in developing human airway smooth muscle. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.28115