Abstract

Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs) involves interactions between Ca2+ influx and release pathways. Depletion of sarcoplasmic reticulum (SR) Ca2+ content activates the Ca2+ sensor, stromal interacting molecule (STIM), which induces store‐operated Ca2+ entry (SOCE). Previous studies on SOCE focused on inositol 1,4,5‐trisphosphate receptor (IP3R)‐ related pathways and how ryanodine receptor (RyR)‐gated store regulates SOCE remained largely unknown. Here we characterized the RyR‐gated SOCE in rat PASMCs. Intracellular Ca2+ was measured in the presence of 1 μM nifedipine to prevent voltage‐dependent Ca2+ entry and extracellular Ca2+ was introduced to induce SOCE after 20‐minute store depletion in Ca2+‐free environment. The RyR agonist, 4‐chloro‐m‐cresol (4‐CmC; 1mM), induced SOCE in rat PASMCs. This Ca2+ response was blocked by a low concentration of the SOCE inhibitor, Gd3+ (1 μM). The RyR1 and RyR3 inhibitor, dantrolene (30 μM), did not inhibit 4‐ CmC‐induced SOCE. In addition, maurocalcine (400 nM), a RyR1 agonist, failed to induce RyR‐gated Ca2+ release in rat PASMCs and hence did not activate SOCE. These data shows that RyR2 is the major RyR subtype that mediates SOCE in rat PASMCs. (This project is supported by NIH grant NL‐071835)

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