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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors.
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Plasma membrane calcium pumps in smooth muscle: from fictional molecules to novel inhibitors.

机译:平滑肌中的质膜钙泵浦:从虚构分子到新型抑制剂。

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摘要

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.
机译:质膜Ca2 +泵(PMCA泵)是Ca2 + -Mg2 + ATPase,可将Ca2 +从细胞质中排出到细胞外空间,对细胞存活和功能至关重要。 PMCA泵由基因PMCA1,-2,-3和-4编码。选择性剪接导致大量同工型,这些同工型的动力学和钙调蛋白以及蛋白激酶A和C的激活方式不同。4个基因的表达和多因素调节提供了冗余,即使存在遗传缺陷也可以使动物存活。消融任何PMCA基因的杂合子小鼠存活,只有消融PMCA1的纯合子小鼠具有胚胎致死性。一些PMCA亚型也可能与其他细胞功能有关。 PMCA泵的生化和生物物理研究受到其低水平表达的限制。很难描述PMCA泵的确切生理作用,因为大多数细胞还表达肌浆/内质网Ca2 +泵和Na + -Ca2 +交换剂,两者均可降低胞质Ca2 +。该领域的主要限制是缺乏PMCA泵的特异性抑制剂。最近,出现了一种名为钙氧还蛋白的抑制剂,这些抑制剂可能有助于描述PMCA泵的作用。

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