Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction

Agonist-induced increases in cytosolic Ca2+ concentration ([Ca2+](cyt)) in pulmonary artery (PA) smooth muscle cells (SMCs) consist of a transient Ca2 + release from intracellular stores followed by a sustained Ca2+ influx. De pletion of intracellular Ca2+ stores triggers capacitative Ca2+ entry (CCE) , which contributes to the sustained increase in [Ca2+](cyt) and the refill ing of Ca2+ into the stores. In isolated PAs superfused with Ca2+-free solu tion, phenylephrine induced a transient contraction, apparently by a rise i n [Ca2+](cyt) due to Ca2+ release from the intracellular stores. The transi ent contraction lasted for 3-4 min until the Ca2+ store was depleted. Resto ration of extracellular Ca2+ in the presence of phentolamine produced a con traction potentially due to a rise in [Ca2+](cyt) via CCE. The store-operat ed Ca2+ channel blocker Ni2+ reduced the store depletion-activated Ca2+ cur rents, decreased CCE, and inhibited the CCE-mediated contraction. In single PASMCs, we identified, using RT-PCR, five transient receptor potential gen e transcripts. These results suggest that CCE, potentially through transien t receptor potential-encoded Ca2+ channels, plays an important role in agon ist-mediated PA contraction.