Role of InsP₃ and ryanodine receptors in the activation of capacitative Ca²⁺ entry by store depletion or hypoxia in canine pulmonary arterial smooth muscle cells

Abstract

Background and purpose: Experiments were performed to determine if capacitative Ca 2 þ entry (CCE) in canine pulmonary arterial smooth muscle cells (PASMCs) is dependent on InsP 3 receptors or ryanodine receptors as induction of CCE is dependent on simultaneous depletion of the functionally separate InsP 3 -and ryanodine-sensitive sarcoplasmic reticulum (SR) Ca 2 þ stores in these cells. Experimental approach: Myocytes were isolated from canine pulmonary arteries using enzymatic procedures and were used within 8 h of preparation. Measurements of cytosolic Ca 2 þ were made by imaging fura-2 loaded individual myocytes that were perfused with physiological buffered saline solution with or without Ca 2 þ .

Hypoxia Induces Intracellular Ca2+ Release by Causing Reactive Oxygen Species-Mediated Dissociation of FK506-Binding Protein 12.6 from Ryanodine Receptor 2 in Pulmonary Artery Myocytes

“…We and other investigators have shown that Ca 2þ release from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) plays an important role in the hypoxic increase in [Ca 2þ ] i in PASMCs and HPV (3,4,7,12,13,19,25,31,32). The importance of RyRs in hypoxic responses in PASMCs is reinforced by findings that Ca 2þ release from the SR is likely to inhibit voltage-dependent K þ channels (15,22) and to open storeoperated Ca 2þ channels (13,14), which cause extracellular Ca 2þ influx, thus providing a positive feedback mechanism to enhance the hypoxic increase in [Ca 2þ ] i and contraction.…”

Inositol trisphosphate receptors in smooth muscle cells

“…Collectively, IP 3 R-mediated Ca 2ϩ release regulates spontaneous and agonist-induced contraction of vascular and nonvascular SMCs. IP 3 R activation and the resulting SR Ca 2ϩ store depletion also stimulated SOCE channel-dependent Ca 2ϩ influx, which induced contraction of SMCs of aorta, inferior vena cava, cremaster, and pulmonary arteries (107, 108,160,177,220,250). IP 3 R activation has also been reported to induce relaxation of certain SMC types (15,102).…”

“…TRPC channels, including 1, 5, 6, and 7 contribute to SOCE in SMCs of coronary and mesenteric arteries and portal vein (186,207). IP 3 R-mediated SR Ca 2ϩ depletion activated TRPC-dependent SOCE in SMCs of inferior vena cava, portal vein, and pulmonary arteries (108,114,160,180).…”

ROS-Dependent Signaling Mechanisms for Hypoxic Ca2+Responses in Pulmonary Artery Myocytes

“…The importance of RyR-mediated Ca 2þ release in hypoxic responses in PASMCs is reinforced by the findings that hypoxic inhibition of K V channels is likely to be secondary to Ca 2þ release from the SR (21, 65, 92). Moreover, hypoxic Ca 2þ release through RyRs may result in the opening of SOC channels, which causes not only extracellular Ca 2þ influx through the opening channels, but also may result in membrane depolarization, activation of Ca V channels, and further Ca 2þ influx, providing a positive-feedback mechanism that enhances hypoxic increase in [Ca 2þ ] i and contraction in PASMCs (58,59).…”