Receptor expression modulates calcium-sensing receptor mediated intracellular Ca2+ mobilization

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Calcium-sensing receptors (CaSRs) are G protein-coupled receptors that regulate calcium homeostasis.
• CaSRs respond to extracellular calcium (Cao2+), L-amino acids, and drugs like cinacalcet.
• The impact of varying CaSR expression levels on cellular signaling is not well understood.

Purpose of the Study:

• To investigate how CaSR expression levels influence CaSR-mediated signaling.
• To analyze intracellular calcium (Cai2+) responses in single cells under different CaSR expression conditions.

Main Methods:

• Utilized a tetracycline-inducible expression system to control CaSR levels.
• Focused on intracellular calcium (Cai2+) responses in single cells.
• Examined both population and single-cell behavior.

Main Results:

• Increased CaSR expression enhanced Cai2+ mobilization in response to Cao2+, L-phenylalanine, and cinacalcet.
• Higher CaSR expression lowered activation thresholds and increased the proportion of responding cells.
• CaSR expression modulated the frequency of Cai2+ oscillations, with cinacalcet and Cao2+ being more effective than L-phenylalanine.

Conclusions:

• Receptor expression significantly modulates CaSR-mediated signaling at the single-cell level.
• Upregulation of CaSR expression can enhance cellular responses and recruit quiescent cells.
• Mechanisms controlling CaSR expression can influence tissue function by altering cellular sensitivity to physiological ligands.