title: Aging-related changes of intracellular Ca2+ stores and contractile response of intestinal smooth muscle.
abstract: In this study, we investigated the effect of aging on intracellular Ca2+ stores, as sarcoendoplasmic reticulum (SR) and mitochondria, and the influence of these compartments on contraction of rat colon smooth muscle [Bitar, K.N., 2003. Aging and neural control of the GI tract V. Aging and gastrointestinal smooth muscle: from signal transduction to contractile proteins. Am. J. Physiol. Gastrointest. Liver. Physiol. 284(1), G1-G7; Marijic, J., Li, Q.X., Song, M., Nishimaru, K., Stefani, E., Toro, L., 2001. Decreased expression of voltage-and Ca2+-activated K+ channels in coronary smooth muscle during aging. Circ. Res. 88, 210-234; Rubio, C., Moreno, A., Briones, A. Ivorra, M.D., D'Ocon, P., Vila, E., 2002. Alterations by age of calcium handling in rat resistance arteries. J. Cardiovasc. Pharmacol. 40(6), 832-840]. Calcium stores and contraction were evaluated by simultaneous measurements of fluorescence and tension in smooth muscle strips loaded with fura-2. Results showed that activation of muscarinic receptors by methylcholine (MCh, 10 microM), induced a greater contraction in aged rats than in adult animals. The inhibition of Ca2+ ATPase by thapsigargin (TG, 1 microM) did not prevent the refilling of SR either in adult or aged rats. MCh, in the presence of TG, induced an increase in transient fluorescence, indicating a release of Ca2+ from TG-insensitive compartment. The mitochondrial uncoupler, FCCP (5 microM), caused a greater increase in intracellular Ca2+ and tension in aged rats, indicating that mitochondria may accumulate more Ca2+ during aging. The present results show that changes in intracellular Ca2+ stores, such as mitochondria and SR, affect contraction and may cause dysfunctions during aging that could culminate in severe alterations of Ca2+ homeostasis and cell damage.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, Rua Três de Maio-100, São Paulo 04044-020, São Paulo, Brazil.
authors.forename: Guiomar S
authors.initials: GS
authors.lastname: Lopes
authors.forename: Alice T
authors.initials: AT
authors.lastname: Ferreira
authors.forename: Maria Etsuko
authors.initials: ME
authors.lastname: Oshiro
authors.forename: Irina
authors.initials: I
authors.lastname: Vladimirova
authors.forename: Neide H
authors.initials: NH
authors.lastname: Jurkiewicz
authors.forename: Aron
authors.initials: A
authors.lastname: Jurkiewicz
authors.forename: Soraya S
authors.initials: SS
authors.lastname: Smaili
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000502:physiology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008931:Mitochondria, Muscle / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; C017506:methylcholine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002794:Choline; D002118:Calcium