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Contractility Measurements of Human Uterine Smooth Muscle to Aid Drug Development
Published on: January 26, 2018
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Calcium sensing receptor in developing human airway smooth muscle
Anne M Roesler1, Sarah A Wicher1, Jovanka Ravix1
1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota.
Journal of Cellular Physiology
|January 10, 2019
Summary
The calcium-sensing receptor (CaSR) is more active in fetal airway smooth muscle (fASM), influencing intracellular calcium levels and enhancing airway contractility and proliferation. This suggests CaSR plays a key role in developing airways.
Area of Science:
- Pulmonary physiology
- Cellular biology
- Calcium signaling
Background:
- Airway smooth muscle (ASM) regulation is vital for fetal lung development and function.
- Fetal lungs have a higher extracellular calcium environment, potentially affecting the calcium-sensing receptor (CaSR).
- CaSR is present in embryonic lung mesenchyme and its role in fetal ASM is unexplored.
Purpose of the Study:
- To investigate the role of CaSR in regulating intracellular calcium ([Ca2+]i) in human fetal ASM (fASM).
- To determine if CaSR modulates fASM contractility and proliferation.
- To compare CaSR function in fASM with adult ASM.
Main Methods:
- Utilized cells from 18-22 week human fetal lungs.
- Employed fluorescence Ca2+ imaging to measure intracellular calcium responses.
- Applied traction force microscopy to assess cellular contractility.
- Investigated effects of CaSR agonists/antagonists (R568, NPS2143, spermine) and pathway inhibitors (U73122, Xestospongin C).
Main Results:
- CaSR expression and sensitivity to extracellular calcium ([Ca2+]o) were higher in fASM compared to adult ASM.
- Histamine-induced [Ca2+]i responses in fASM were more sensitive to [Ca2+]o, modulated by CaSR agonists/antagonists.
- CaSR activation influenced phospholipase C signaling and store-operated calcium entry.
- fASM contractility and proliferation demonstrated sensitivity to [Ca2+]o and CaSR modulation.
Conclusions:
- A functional CaSR is present in developing human ASM.
- CaSR significantly modulates intracellular calcium levels, contractility, and proliferation in fASM.
- These findings highlight CaSR's critical role in fetal airway development and potential implications for neonatal respiratory diseases.
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