The regulation of the intracellular calcium concentration ([Ca 2+] i) plays an important role in many biological processes. The PMCA allows the expulsion of Ca2+ out of the cell with high affinity but low capacity. To better understand its role in the secretion of insulin we studied them in pancreatic β cell. PMCA has four (4) isoforms whose PMCA1-4 which each comprise three (3) alternative splice sites A, B and C that will generate different splice variants. In purified β cells, in the RINm5F cells and in rat pancreatic islet cells, we identified the rPMCA1xb, rPMCA2yb, rPMCA2wb, rPMCA3za, rPMCA3zc and rPMCA4xb. Two additional isoforms have been found in the islet cells, so in non β cells of the islets of Langerhans, it is the rPMCA1xkb and rPMCA4za. Whereas isoforms 1 and 4 are expressed in most tissues, isoforms 2 and 3 are expressed within specialized tissues. The presence of these specialized isoforms in islets indicates that the regulation of calcium homeostasis in these cells is specific and requires specialized ATPases. The β cell is equipped with a variety of PMCAs regulated differently, which gives the PMCA different possibility of regulation of calcium homeostasis.

The increase in intracellular calcium concentration ([Ca2+]i) represents a major event in the process of insulin secretion. The Plasma Membrane Calcium ATPase (PMCAs) are equipped with a series of isoforms that may be tissue specific. It has been suggested that there might be a difference in activity between the isoforms and that some of them could play a fundamental role in the operation of the β cell. The PMCAs are regulated by calmodulin (CaM), the phospholipid acid, protein kinase, protease, and G protein, and by oligomerisation. CaM activates the pump and this activation effect will be limited by alternative splicing at site C that is their binding domain. Acidic phospholipids are stimulators of PMCA. But, alternative splicing at site A could therefore affect the regulation of PMCA isoforms by phospholipids by altering accessibility of phospholipids to their binding domain. In contrast, the PMCAs are inhibited by lanthanum and vanadate ions, by calmodulin antagonists, N-ethylmaleimide and derivatives of fluorescein. However, the experiments conducted showed that the suppression of the oscillations of [Ca2+] i is accompanied by an increase in glucose metabolism and insulin secretion but which continues to oscillate at a lower frequency. This allowed to say that the oscillations of [Ca2 +]i are not directly involved in the process of oscillations of insulin secretion but could intervene in its fine regulation.