FIGURE 12.

Functional interaction of membrane receptor with ion channels in the plasma membrane via second messengers is important to link extracellular stimuli to the regulation of cell functions (e.g., contraction, migration, proliferation, apoptosis, and differentiation). This schematic diagram depicts the interaction of Ca²⁺-sensing receptor (CaSR), a unique G protein-coupled receptor (GPCR), with receptor-operated and mechanosensitive cation channels of TRPC6 via the second messenger diacylglycerol (DAG). CaSR can be activated by cations (e.g., Ca²⁺, Mg²⁺, Gd³⁺); amino acids like phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), and glutamic acid (Glu); antibiotics like neomycin and streptomycin; and amyloid-β peptide. Activation of CaSR not only stimulates TRPC6 channels to induce extracellular Ca²⁺-mediated intracellular Ca²⁺ increase to induce pulmonary arterial smooth muscle cell (PASMC) contraction, migration, and proliferation but also activates the RAS/MAPK signaling pathway to reinforce its mitogenic effect. [Ca²⁺]_cyt, cytosolic free Ca²⁺ concentration. CSD, caveolin scaffolding domain; MLC, myosin light chain.