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Translocon closure to Ca2+ leak in proliferating vascular smooth muscle cells

By Mohamed S Amer, Jing Li, David J. O'Regan, Derek S. Steele, Karen E. Porter, Asipu Sivaprasadarao and David J. Beech

Abstract

Vascular smooth muscle cells have a proliferative phenotype that is important in vascular development, adaptation, and disease. Intracellular calcium handling is thought to play pivotal roles in determining the properties of these cells, and thus previously unrecognized mechanisms for transmembrane calcium movement are of potential interest. An unsolved question is the mechanism of constitutive (passive) calcium leak from the intracellular stores. Studies of other cell types have suggested that the translocon is a calcium leak pathway. Here we investigated the contribution of the translocon in proliferating vascular smooth muscle cells. Calcium leak into the cytoplasm was measured using fura-2, and protein synthesis was measured using radioactive methionine. Puromycin, emetine, and anisomycin are chemicals that inhibit protein synthesis, acting via the translocon; all three agents strongly inhibited protein synthesis in the smooth muscle cells within 1 h. Puromycin, which opens the translocon, evoked a transient increase in cytoplasmic calcium that was similar in amplitude to the calcium rise evoked by thapsigargin. The puromycin effect was abolished by thapsigargin. The treatment of cells for 1 h with emetine or anisomycin, which close the translocon, inhibited the calcium release evoked by puromycin but not the calcium release evoked by extracellular ATP, endothelin-1, or the calcium ionophore ionomycin. Thapsigargin-evoked calcium rises were slightly suppressed by emetine but unaffected by puromycin or anisomycin. The data suggest that the translocon has the capacity to act as a calcium leak pathway in the ribosomal endoplasmic reticulum but that it is normally closed and lacks relevance to physiological calcium leak mechanisms

Topics: Articles
Publisher: American Physiological Society
OAI identifier: oai:pubmedcentral.nih.gov:2670693
Provided by: PubMed Central
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