Histamine-mediated increases in cytosolic [Ca ] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells

Mauban, Joseph R. H., Katherine Wilkinson, Christian Schach, and Jason X.-J. Yuan. Histamine-mediated increases in cytosolic [Ca ] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells. Am J Physiol Cell Physiol 290: C325–C336, 2006. First published September 14, 2005; doi:10.1152/ajpcell.00236.2005.—Agonist stimulation of human pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) with histamine showed similar spatiotemporal patterns of Ca release. Both sustained elevation and oscillatory patterns of changes in cytosolic Ca concentration ([Ca ]cyt) were observed in the absence of extracellular Ca . Capacitative Ca entry (CCE) was induced in PASMC and PAEC by passive depletion of intracellular Ca stores with 10 M cyclopiazonic acid (CPA; 15–30 min). The pyrazole derivative BTP2 inhibited CPA-activated Ca influx, suggesting that depletion of CPA-sensitive internal stores is sufficient to induce CCE in both PASMC and PAEC. The recourse of histaminemediated Ca release was examined after exposure of cells to CPA, thapsigargin, caffeine, ryanodine, FCCP, or bafilomycin. In PASMC bathed in Ca -free solution, treatment with CPA almost abolished histamine-induced rises in [Ca ]cyt. In PAEC bathed in Ca -free solution, however, treatment with CPA eliminated histamine-induced sustained and oscillatory rises in [Ca ]cyt but did not affect initial transient increase in [Ca ]cyt. Furthermore, treatment of PAEC with a combination of CPA (or thapsigargin) and caffeine (and ryanodine), FCCP, or bafilomycin did not abolish histamine-induced transient [Ca ]cyt increases. These observations indicate that 1) depletion of CPA-sensitive stores is sufficient to cause CCE in both PASMC and PAEC; 2) induction of CCE in PAEC does not require depletion of all internal Ca stores; 3) the histamine-releasable internal stores in PASMC are mainly CPA-sensitive stores; 4) PAEC, in addition to a CPA-sensitive functional pool, contain other stores insensitive to CPA, thapsigargin, caffeine, ryanodine, FCCP, and bafilomycin; and 5) although the CPA-insensitive stores in PAEC may not contribute to CCE, they contribute to histamine-mediated Ca release.