Contrasting effects of hypoxia on cytosolic Ca2+ spikes in conduit and resistance myocytes of the rabbit pulmonary artery

1. The effects of hypoxia on cytosolic Ca2+ ([Ca2+](i)) and spontaneous cytosolic Ca2+ spikes were examined in fura 2-loaded myocytes isolated from conduit and resistance branches of the rabbit pulmonary artery. In all myocyte classes, generation or the Ca2+ spikes was modulated by basal [Ca2+](i) which, in turn, was influenced by the influx of Ca2+ through L-type Ca2+ channels of the plasmalemma. 2. Conduit and resistance myocytes responded distinctly to hypoxia. In most conduit myocytes (similar to 82% of total; n = 23) exposure to hypoxia reduced basal [Ca2+](i). This effect was often associated with the abolition of the Ca2+ spikes. Hypoxia gave rise to two main responses in resistance myocytes. In a subset of resistance myocytes (41% of total; n = 34) hypoxia incremented basal [Ca2+](i) but reduced Ca2+ spike amplitude. This response mimicked the effect of membrane depolarization with K+ and was reverted by nifedipine or the removal of extracellular Ca2+. In a second subset of resistance myocytes (59% of total; n = 34) hypoxia decreased basal [Ca2+](i) and, in most cases, increased spike amplitude; a response counteracted by depolarization with K+. 3. These results indicate that hypoxia can differentially modulate [Ca2+](i) in smooth muscle cells from large and small diameter pulmonary vessels through a,dual effect on transmembrane Ca2+ influx. Our observations further demonstrate the longitudinal heterogeneity of myocytes along the pulmonary arterial tree and help to explain the hypoxia vasomotor responses in the pulmonary circulation.