Capacitative Ca2+entry in agonist-induced pulmonary vasoconstriction

Abstract

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. Depletion of intracellular Ca²⁺stores triggers capacitative Ca²⁺entry (CCE), which contributes to the sustained increase in [Ca²⁺]_cytand the refilling of Ca²⁺into the stores. In isolated PAs superfused with Ca²⁺-free solution, phenylephrine induced a transient contraction, apparently by a rise in [Ca²⁺]_cytdue to Ca²⁺release from the intracellular stores. The transient contraction lasted for 3–4 min until the Ca²⁺store was depleted. Restoration of extracellular Ca²⁺in the presence of phentolamine produced a contraction potentially due to a rise in [Ca²⁺]_cytvia CCE. The store-operated Ca²⁺channel blocker Ni²⁺reduced the store depletion-activated Ca²⁺currents, decreased CCE, and inhibited the CCE-mediated contraction. In single PASMCs, we identified, using RT-PCR, five transient receptor potential gene transcripts. These results suggest that CCE, potentially through transient receptor potential-encoded Ca²⁺channels, plays an important role in agonist-mediated PA contraction.