Functional coupling of the Na+/Ca2+ exchanger with Ca2+ release from intracellular stores in cultured smooth muscle cells of guinea pig ileum.
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 microM), but not nicardipine (10 microM), 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 Na+/Ca2+ exchanger can release Ca2+ from the thapsigargin-sensitive intracellular stores including IP3-releasable pools.
Ohata
H
H
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Kawanishi
T
T
Hisamitsu
T
T
Takahashi
M
M
Momose
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D012965:Sodium Chloride; D002794:Choline; D002118:Calcium