DiPolo Reinaldo, Beaugé Luis
Laboratorio de Fisiología Celular, Centro de Biofísica y Bioquímica, IVIC, Apartado 21827, Caracas 1020A, Venezuela.
Pflugers Arch. 2008 Jun;456(3):623-33. doi: 10.1007/s00424-007-0430-0. Epub 2008 Jan 3.
In squid axons, intracellular Mg2+ reduces the activity of the Na+/Ca2+ exchanger by competing with Ca2+ i for its regulatory site. The state of the Ca i-regulatory site (active-inactive) also alters the apparent affinity of intra- and extracellular transport sites. Conditions that hinder the binding of Ca2+ i (low pH i, low [Ca2+]i, high [Mg2+]i) diminish the apparent affinity of intracellular transport sites, in particular for Na i due to its synergism with H+ inhibition, but less noticeably for Ca2+ i because of its antagonism towards (Ha i + Na+ i) and Mg2+ i inhibitions. These are kinetic effects unrelated to the true affinity of the sites. With the Ca i-regulatory site saturated, the intracellular transporting sites are insensitive to [H+]i and to ATP. Likewise, the state of the Ca i-regulatory site (activated or inactivated) influences the affinity of the extracellular Ca o and Na o-transport sites (trans effects). In this case, the effects are opposite to those predicted by any of the transport schemes proposed for the Na+/Ca2+exchanger; i.e. its mechanism remains unexplained. In addition to their intrinsic importance for a full understanding of the properties of the Na+/Ca2+ exchanger, these findings show a new way by which the state of the Ca i-regulatory site may determine net movements of Ca2+ through this system.
在鱿鱼轴突中，细胞内的Mg2+通过与Ca2+ i竞争其调节位点来降低Na+/Ca2+交换体的活性。Ca i调节位点的状态（激活-失活）也会改变细胞内和细胞外转运位点的表观亲和力。阻碍Ca2+ i结合的条件（低pH i、低[Ca2+]i、高[Mg2+]i）会降低细胞内转运位点的表观亲和力，特别是对Na i而言，由于其与H+抑制的协同作用，但对Ca2+ i的影响不太明显，因为它对（Hai + Na+ i）和Mg2+ i抑制具有拮抗作用。这些是与位点的真实亲和力无关的动力学效应。当Ca i调节位点饱和时，细胞内转运位点对[H+]i和ATP不敏感。同样，Ca i调节位点的状态（激活或失活）会影响细胞外Ca o和Na o转运位点的亲和力（反式效应）。在这种情况下，这些效应与为Na+/Ca2+交换体提出的任何转运模式所预测的效应相反；即其机制仍无法解释。除了对于全面理解Na+/Ca2+交换体的特性具有内在重要性之外这些发现还揭示了一种新的方式，通过这种方式Ca i调节位点的状态可能决定Ca2+通过该系统的净移动。
