Mitochondrial involvement in carbachol-induced intracellular Ca2+ mobilization and contraction in rat gastric smooth muscle
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2011-11-21
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Corrêa, Roberta Moreira 
Pereira, Gustavo José da Silva
Hirata, Hanako
Garcez-do-Carmo, Lúcia
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Aims: Mitochondria are important modulators of Ca2+ homeostasis. However, it is not clear if they modulate and participate in smooth muscle signaling and contraction. the aim of the present work was to investigate the role of mitochondria in Ca2+ transients and contraction induced by metabotropic muscarinic receptor activation in rat gastric smooth muscle.Main methods: Carbachol (CC11)-induced contraction was investigated in the absence or presence of increasing concentration of mitochondrial protonophore, carbonyl cyanide p-(trifluoro-methoxy)phenyl-hydrazone (FCCP), in gastric fundus strips. Ca2+ and mitochondrial membrane potential (Delta Psi m) measurements were performed in primarily cultured gastric smooth muscle cells loaded with FURA-2 or TMRE dyes.Key findings: Results show that CCh (1 mu M)-induced contraction was inhibited by FCCP in a concentration-dependent manner. in cultured smooth muscle cells CCh (1 mu M) caused a cytosolic Ca2+ rise. Preincubation with FCCP strongly inhibited CCh-evoked Ca2+ transients indicating that mitochondria shape intracellular Ca2+ Signals. CCh induced elevations of Delta Psi m in 60% of the individual mitochondrion analyzed.Significance: Taken together our results indicate that CCh induces release of Ca2+ from intracellular stores, which may be modulated by mitochondria. Thus, mitochondria participate of the intracellular Ca2+ homeostasis in muscarinic contraction in gastric fundus smooth muscle. (C) 2011 Elsevier Inc. All rights reserved.
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Life Sciences. Oxford: Pergamon-Elsevier B.V., v. 89, n. 21-22, p. 757-764, 2011.