title: Mitochondrial involvement in carbachol-induced intracellular Ca2+ mobilization and contraction in rat gastric smooth muscle.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Carbachol (CCh)-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 (ΔΨm) measurements were performed in primarily cultured gastric smooth muscle cells loaded with FURA-2 or TMRE dyes.
  
  
  RESULTS
  Results show that CCh (1 μM)-induced contraction was inhibited by FCCP in a concentration-dependent manner. In cultured smooth muscle cells CCh (1 μM) 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 ∆Ψm in 60% of the individual mitochondrion analyzed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Paulista School of Medicine, Federal University of São Paulo (UNIFESP/EPM), Brazil.
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Correa
authors.forename: Simone S L
authors.initials: SS
authors.lastname: Lafayette
authors.forename: Gustavo J S
authors.initials: GJ
authors.lastname: Pereira
authors.forename: Hanako
authors.initials: H
authors.lastname: Hirata
authors.forename: Lúcia
authors.initials: L
authors.lastname: Garcez-do-Carmo
authors.forename: Soraya S
authors.initials: SS
authors.lastname: Smaili
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000187:drug effects; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D011976:Receptors, Muscarinic; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002217:Carbachol; D002118:Calcium