Mooren F C, Turi S, Gunzel D, Schlue W R, Domschke W, Singh J, Lerch M M
Department of Medicine B, Westfälische Wilhelms-Universität, Münster, Germany.
FASEB J. 2001 Mar;15(3):659-72. doi: 10.1096/fj.00-0172com.
Although the role of calcium (Ca2+) in the signal transduction and pathobiology of the exocrine pancreas is firmly established, the role of magnesium (Mg2+) remains unclear. We have characterized the intracellular distribution of Mg2+ in response to hormone stimulation in isolated mouse pancreatic acinar cells and studied the role of Mg2+ in modulating Ca2+ signaling using microspectrofluorometry and digital imaging of Ca2+- or Mg2+-sensitive fluorescent dyes as well as Mg2+-sensitive intracellular microelectrodes. Our results indicate that an increase in intracellular Mg2+ concentrations reduced the cholecystokinin (CCK) -induced Ca2+ oscillations by inhibiting the capacitive Ca2+ influx. An intracellular Ca2+ mobilization, on the other hand, was paralleled by a decrease in [Mg2+]i, which was reversible upon hormone withdrawal independent of the electrochemical gradients for Mg2+, Ca2+, Na+, and K+, and not caused by Mg2+ efflux from acinar cells. In an attempt to characterize possible Mg2+ stores that would explain the reversible, hormone-induced intracellular Mg2+ movements, we ruled out mitochondria or ATP as potential Mg2+ buffers and found that the CCK-induced [Mg2+]i decrease was initiated at the basolateral part of the acinar cells, where most of the endoplasmic reticulum (ER) is located, and progressed from there toward the apical pole of the acinar cells in an antiparallel fashion to Ca2+ waves. These experiments represent the first characterization of intracellular Mg2+ movements in the exocrine pancreas, provide evidence for possible Mg2+ stores in the ER, and indicate that the spatial and temporal distribution of intracellular Mg concentrations profoundly affects acinar cell Ca2+ signaling.
尽管钙（Ca2+）在外分泌胰腺的信号转导和病理生物学中的作用已得到明确证实，但镁（Mg2+）的作用仍不清楚。我们已对分离的小鼠胰腺腺泡细胞中激素刺激下Mg2+的细胞内分布进行了表征，并使用Ca2+或Mg2+敏感荧光染料的显微光谱荧光测定法和数字成像以及Mg2+敏感的细胞内微电极研究了Mg2+在调节Ca2+信号传导中的作用。我们的结果表明，细胞内Mg2+浓度的增加通过抑制电容性Ca2+内流降低了胆囊收缩素（CCK）诱导的Ca2+振荡。另一方面，细胞内Ca2+的动员与[Mg2+]i的降低同时发生，这种降低在激素撤除后是可逆的，与Mg2+、Ca2+、Na+和K+的电化学梯度无关，且不是由腺泡细胞中Mg2+外流引起的。为了表征可能解释激素诱导的可逆细胞内Mg2+运动的Mg2+储存库，我们排除了线粒体或ATP作为潜在的Mg2+缓冲剂，并发现CCK诱导的[Mg2+]i降低始于腺泡细胞的基底外侧部分，此处是大部分内质网（ER）所在的位置，并以与Ca2+波相反的方式从那里向腺泡细胞的顶端极发展。这些实验首次表征了外分泌胰腺中细胞内Mg2+的运动，为内质网中可能存在Mg2+储存库提供了证据，并表明细胞内Mg浓度的时空分布深刻影响腺泡细胞的Ca2+信号传导。
