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This Article Full Text Full Text (PDF) All Versions of this Article: 298/2/L178    most recent 00134.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, T. Articles by Hu, Q. PubMed PubMed Citation Articles by Chen, T. Articles by Hu, Q.

Mitochondria depletion abolishes agonist-induced Ca²⁺ plateau in airway smooth muscle cells: potential role of H₂O₂

¹Department of Pathophysiology, ; ²Key Laboratory of Pulmonary Diseases of Ministry of Health of China, and ; ³Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan; and ; ⁴Department of Respiratory Medicine, Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China

Submitted 20 April 2009 ; accepted in final form 18 November 2009

The mechanisms by which mitochondria regulate the sustained phase of agonist-induced responses in cytosolic Ca²⁺ concentration as an independent organelle in whole is not clear. By exposing to ethidium bromide and supplying pyruvate and uridine, we established mitochondrial DNA (mtDNA)-depleted rat airway smooth muscle cells (RASMCs) with maintained cellular energy. Upon an exposure to 2 µM histamine, [Ca²⁺]_i in control RASMCs increased to a peak followed by a plateau above baseline, whereas [Ca²⁺]_i in mtDNA-depleted RASMCs jumped to a peak and then declined to baseline without any plateau. mtDNA depletion apparently attenuated intracellular reactive oxygen species generation induced by histamine. By coexposure to 2 µM histamine and 0.1 µM exogenous H₂O₂, which did not affect [Ca²⁺]_i by itself, the above difference in [Ca²⁺]_i kinetics in mtDNA-depleted RASMCs was reversed. Intracellular H₂O₂ decomposition abolishes histamine-induced sustained elevation in [Ca²⁺]_i in RASMCs. Thus, mitochondria regulate agonist-induced sustained [Ca²⁺]_i elevation by a H₂O₂-dependent mechanism.

histamine; calcium; reactive oxygen species