title: Effects of hypoxia and mitochondrial inhibition on the capacitative calcium entry in rabbit pulmonary arterial smooth muscle cells.
abstract: We have investigated the effects of hypoxia and mitochondria inhibitors on the capacitative Ca(2+) entry (CCE) in cultured smooth muscle cells from rabbit small pulmonary arteries. Cyclopiazonic acid (CPA) depleted Ca(2+) from sarcoplasmic reticulum (SR) in Ca(2+)-free medium and subsequent addition of Ca(2+) led to the nifedipine-insensitive, La(3+)-sensitive Ca(2+) influx. The presence of CCE was further verified by the measurement of unidirectional Mn(2+) influx. During the decay phase of the CCE-induced [Ca(2+)]c transients, hypoxia (P(O2) < 50 mmHg) and the mitochondria inhibitor FCCP reversibly increased [Ca(2+)]c, that is La(3+)-sensitive. Once SR is depleted by CPA, subsequent treatment of FCCP slowed the decay of CCE-induced [Ca(2+)]c transients but it did not attenuate Mn(2+) influx. Mitochondrial uptake of incoming Ca(2+) through CCE was demonstrated by additional increase in [Ca(2+)]c with Ca(2+) ionophore after terminating CCE. Together, it is suggested that the augmentation of CCE-induced [Ca(2+)]c transients by hypoxia and FCCP reflects a net gain of [Ca(2+)]c by the inhibition of mitochondrial Ca(2+) uptake.
authors.affiliation: Department of Physiology, Sungkyunkwan University, School of Medicine, 300 Chunchundong, Changanku, 440-746, Suwon, South Korea.
authors.forename: Tong Mook
authors.initials: TM
authors.lastname: Kang
authors.forename: Myoung Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Uhm
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D016257:Fura-2; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007811:Lanthanum; D008345:Manganese / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D007211:Indoles; D014475:Uncoupling Agents; D014665:Vasodilator Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D008345:Manganese; D007811:Lanthanum; D002118:Calcium; D016257:Fura-2; C000543:cyclopiazonic acid