Characterization of Ca2+ oscillations in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension

A rise in cytosolic Ca2+ ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC proliferation, two major causes for elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). The rise in [Ca2+]cyt is mainly induced by Ca2+ release and Ca2+ influx. Under the resting conditions, we observed spontaneous and periodic increases in [Ca2+]cyt, or Ca2+ oscillations, in some (<5%) normal PASMC. Interestingly, 50% of IPAH‐PASMC showed spontaneous Ca2+ oscillations. The amplitude of spontaneous Ca2+ oscillations in IPAH‐PASMC was 5‐fold larger than in normal PASMC. Removal of extracellular Ca2+ abolished the Ca2+ oscillations in IPAH‐PASMC, while 10 μM La3+ significantly decreased the amplitude and frequency of the Ca2+ oscillations. Furthermore, application of OAG (100 μM), a membrane‐permeable diacylglycerol analogue, slightly increased [Ca2+]cyt in 30% of normal PASMC, but elicited a large increase in [Ca2+]cyt followed, sometimes, by Ca2+ oscillations in most IPAH‐PASMC. In summary, human PASMC possess spontaneous and OAG‐induced Ca2+ oscillations. The amplitude and frequency of the Ca2+ oscillations are enhanced in IPAH‐PASMC, which may contribute to the sustained vasoconstriction and vascular remodeling in patients with IPAH. NIH grants: HL 066012 and HL 098053.