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

Chen T, Zhu L, Wang T, Ye H, Huang K, Hu Q. Mitochondria depletion abolishes agonist-induced Ca2+ plateau in airway smooth muscle cells: potential role of H2O2. Am J Physiol Lung Cell Mol Physiol 298: L178-L188, 2010. First published November 20, 2009; doi: 10.1152/ajplung.00134.2009.-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 mu M 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 mu M histamine and 0.1 mu M 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.