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The Role of Na(superscript +)/Ca(superscript 2+) Exchanger in Modulating Calcium Homeostasis in Bovine Chromaffin Cell

鈉鈣交換蛋白對牛嗜鉻細胞鈣離子恆定之調控

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摘要


嗜鉻細胞受到乙醯膽鹼刺激時,造成鈉離子湧入,並開啓電位閘門通道。自電位閘門通道湧入的鈣離子,會引發CICR,造成細胞內鈣離子濃度大量上升,促進胞吐作用的進行。同時,自乙醯膽鹼受器湧入的鈉離子,會讓鈉鈣交換蛋白短暫地反轉,貢獻一部份的鈣離子湧入。我們發現用Thapsigargin排空內質網會降低鈉鈣交換蛋白反轉所引起的[Ca(上標 2+)]c上升。此外,處理Ryanodine受器抑制劑Ryanodine或IP3受器抑制劑2-APB也皆能減少[Ca(上標 2+)]c之上升量。若同時處理Ryanodine及2-APB,其結果與單獨處理2-APB無顯著差異。這些結果表示鈉鈣交換蛋白反轉的確能夠使內質網從Ryanodine受器與IP3受器釋放鈣離子,且IP3受器可能扮演調控Ryanodine受器開啓的角色。鈉鈣交換蛋白和Ryanodine受器、IP3受器之間的互動對細胞內鈣離子恆定有重要影響。

並列摘要


Bovine chromaffin cells can be stimulated by acetylcholine to allow Na(superscript +) influx and the opening of voltage-gated Ca(superscript 2+) channels (VGCC). Ca2+ entry via VGCC dramatically increases [Ca(superscript 2+)]c by the process of Ca(superscript 2+)-induced Ca(superscript 2+) release (CICR) and the increase in [Ca(superscript 2+)]c promotes exocytosis. At the same time, Na(superscript +) influx through acetylcholine receptor temporarily induces the reverse mode activity of Na(superscript +)/Ca(superscript 2+) exchanger (NCX), which also contributes to part of Ca(superscript 2+) influx. It is controversial whether the reverse mode of NCX also can promote CICR. Here our results show that the elevation of [Ca(superscript 2+)]c by the reverse mode of NCX was inhibited by emptying ER with Thapsigargin. Besides, [Ca(superscript 2+)]c rising could be inhibited by the treatment of either Ryanodine (Ry), a Ryanodine receptor (RyR) inhibitor or 2-APB, an IP3 receptor (IP3R) inhibitor. The effect of treating 2-APB and Ry simultaneously had no significant difference from that of treating 2-APB alone. We concluded that the reverse mode of NCX can promote the release of Ca(superscript 2+) from ER through RyR and IP3 receptor (IP3R). Furthermore, IP3R may function as a modulator of the opening of RyR. The crosstalk of NCX, RyR, and IP3R has important effects on intracellular calcium homeostasis.

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