Interaction between NCX and SERPA in Ca²⁺ signaling in human endothelial cells

The interaction between sodium-calcium-exchanger (NCX) and the endoplasmic reticulum (ER) with respect to Ca²⁺ signaling was studied using fura-2 fluorescence imaging microscopy in human endothelial cells. The inflammatory agonist histamine was used to increase the intracellular Ca²⁺ concentration. Under resting conditions, the endothelial NCX serves to unload some of the Ca²⁺ content accumulated in the ER. This unloading is important in order to maintain the buffer barrier function of the peripheral ER. Application of histamine (1 uM) in the presence of extracellular Ca²⁺ caused a long lasting Ca²⁺ response. This maintained response is dependent on the state of ER Ca²⁺ content, which is at least partly refilled by Ca²⁺ entry via NCX working in the reverse mode during the course of agonist stimulation. After cessation of agonist stimulation, a major part of the increased Ca²⁺ is cleared by sarcoplasmic/endoplasmic reticulum Ca²⁺ - ATPase (SERCA) and NCX working in a serial configuration. In summary, in human endothelial cells, NCX can unload or refill the ER and thereby modulate the Ca²⁺ level.Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat