Pathogenic Role of Store-Operated and Receptor-Operated Ca^𝟐+ Channels in Pulmonary Arterial Hypertension

Figure 3

Increased levels of [Ca²⁺]_cyt in PASMC are required for pulmonary vascular remodeling and pulmonary vasoconstriction. When levels of [Ca²⁺]_cyt increase due to influx through various Ca²⁺ channels in the plasma membrane and by depletion of SR/ER stores, Ca²⁺ can bind to calmodulin (CaM) leading to PASMC contraction by activating myosin light chain kinase (MLCK) causing phosphorylation of MLC, resulting in a sliding motion of the actomyosin complex leading to contraction. Additionally, Ca²⁺ activates intracellular Ca²⁺-dependent signal transduction proteins such as CaM kinase (CaMK) and mitogen-activated protein kinase (MAPK), as well as activating other transcription factors (nuclear factor of activated T cells (NFAT, cAMP response element binding protein (CREB), activator protein-1 (AP-1), and nuclear factor (NF-κB) (that trigger PAMSC to enter the cell cycle from a quiescent differentiated state leading to proliferation).