Pande Jyoti, Grover Ashok K
Department of Medicine, McMaster University, Hamilton, ON, Canada.
Can J Physiol Pharmacol. 2005 Aug-Sep;83(8-9):743-54. doi: 10.1139/y05-075.
Plasma membrane Ca2+ pumps (PMCA pumps) are Ca2+-Mg2+ ATPases that expel Ca2+ from the cytosol to extracellular space and are pivotal to cell survival and function. PMCA pumps are encoded by the genes PMCA1, -2, -3, and -4. Alternative splicing results in a large number of isoforms that differ in their kinetics and activation by calmodulin and protein kinases A and C. Expression by 4 genes and a multifactorial regulation provide redundancy to allow for animal survival despite genetic defects. Heterozygous mice with ablation of any of the PMCA genes survive and only the homozygous mice with PMCA1 ablation are embryolethal. Some PMCA isoforms may also be involved in other cell functions. Biochemical and biophysical studies of PMCA pumps have been limited by their low levels of expression. Delineation of the exact physiological roles of PMCA pumps has been difficult since most cells also express sarco/endoplasmic reticulum Ca2+ pumps and a Na+-Ca2+-exchanger, both of which can lower cytosolic Ca2+. A major limitation in the field has been the lack of specific inhibitors of PMCA pumps. More recently, a class of inhibitors named caloxins have emerged, and these may aid in delineating the roles of PMCA pumps.
质膜钙泵（PMCA泵）是一种钙 - 镁ATP酶，可将钙离子从细胞质溶胶排出到细胞外空间，对细胞存活和功能至关重要。PMCA泵由PMCA1、-2、-3和-4基因编码。可变剪接产生大量同工型，它们在动力学以及受钙调蛋白、蛋白激酶A和C激活方面存在差异。4个基因的表达和多因素调节提供了冗余，使得动物即使存在基因缺陷也能存活。任何一个PMCA基因被敲除的杂合小鼠都能存活，只有PMCA1基因被敲除的纯合小鼠胚胎致死。一些PMCA同工型可能还参与其他细胞功能。对PMCA泵的生化和生物物理研究一直受到其低表达水平的限制。由于大多数细胞也表达肌浆网/内质网钙泵和钠 - 钙交换体，二者均可降低细胞质中的钙离子浓度，因此明确PMCA泵的确切生理作用一直很困难。该领域的一个主要限制是缺乏PMCA泵的特异性抑制剂。最近，一类名为钙毒素的抑制剂出现了，它们可能有助于明确PMCA泵的作用。
