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Functional coupling of the exchanger with Ca2+ release from intracellular stores in cultured smooth muscle cells of guinea pig ileum
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文摘
The mechanism of increase in intracellular Ca2+ concentration ([Ca2+]i) by removal of extracellular Na+, which phenomena were reported previously (Japan. J. Pharmacol.63 83-91 1993), was investigated in cultured guinea pig ileum longitudinal muscle cells loaded with a fluorescent Ca2+ indicator, fura-2, by digital ratio imaging microscopy. Isotonic substitution of choline chloride for NaCl induced a transient increase in [Ca2+]i. The pretreatment of thapsigargin (0.5 μM), but not nicardipine (10 μM), suppressed the transient increase completely. In solutions containing micromolar concentrations of free Ca2+ (nominally Ca2+-free solution), the Na+-free induced transient increase was observed, but neither the second cell exposure to the Na+-free solution nor the following application of histamine increased [Ca2+]i, indicating that removal of extracellular Na+ releases Ca2+ from intracellular stores including inositol 1,4,5-trisphosphate (IP3)-releasable pools. The Na+-free-induced transient increase required the presence of more than micromolar concentrations of extracellular free Ca2+ and releasable Ca2+ within the stores, but ryanodine did not affect the transient increase. These results suggest that undetectable influx of Ca2+ by the reverse-mode action of the exchanger can release Ca2+ from the thapsigargin-sensitive intracellular stores including IP3-releasable pools.

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