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 of 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 (approximately 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 hypoxic vasomotor responses in the pulmonary circulation.
Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Facultad de Medicina, Spain.
J
J
Ureña
A
A
Franco-Obregón
J
J
López-Barneo
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D015854:Up-Regulation / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology
D005456:Fluorescent Dyes; D002118:Calcium; D016257:Fura-2