Acute hypoxia increases cytosolic calcium in cultured pulmonary arterial myocytes.
The effects of hypoxia on the cytosolic Ca2+ concentration, [Ca2+]i, were characterized in cultured pulmonary arterial smooth muscle (PASM) cells. Reducing O2 tension (PO2) from 150 to < 25 Torr induced a reversible 100-200% increase in [Ca2+]i that was characterized by two components: an early rise in [Ca2+]i that was dependent on the rate, as well as the magnitude, of decline in PO2 and a later, steady-state increase that was independent of the rate at which PO2 changed. Caffeine lowered [Ca2+]i during normoxia and blocked the early component of the response to hypoxia, whereas the steady-state hypoxic response was only partially inhibited. Like hypoxia, thapsigargin (TG) elevated [Ca2+]i, and there was no additional hypoxia-induced elevation in [Ca2+]i at any time after exposure to TG. At steady state, the hypoxic responses were completely reversed by removal of extracellular Ca2+, whereas, on average, verapamil and nifedipine attenuated the hypoxia-induced increases in [Ca2+]i by only 44 and 35%, respectively. These results suggest that hypoxia-induced elevation of [Ca2+]i in PASM cells consists of an early release of Ca2+ from the sarcoplasmic reticulum and a later influx of extracellular Ca2+, in part, through nifedipine- and verapamil-insensitive Ca2+ channels. The results are consistent with the idea that hypoxia and thapsigargin may share common mechanisms for tonically increasing [Ca2+]i.
Department of Medicine, Baltimore Veterans Affairs Hospital, Maryland.
C G
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Salvaterra
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Goldman
D000208:Acute Disease; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D016257:Fura-2; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D013729:Terpenes; D002110:Caffeine; D019284:Thapsigargin; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D010100:Oxygen; D002118:Calcium; D016257:Fura-2