Mechanisms and significance of cell volume regulation

Mechanisms and significance of cell volume regulation
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DOI:
10.1080/07315724.2007.10719667
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发表时间:
2007-10-01
影响因子:
3.5
通讯作者:
Lang, Florian
Lang, Florian
中科院分区:
医学4区
文献类型:
--
作者:
Lang, Florian

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人类和动物细胞的存活需要避免细胞体积的过度改变。细胞内有机物质的积累所积累的渗透压必须通过降低胞质离子浓度来补偿。Na+/K+ ATP酶将Na+挤出以交换K+,K+可以通过K+通道渗透细胞膜。K+的排出在细胞膜上产生细胞负电位差,驱动阴离子如Cl-的排出。低的细胞溶质Cl-浓度通过有机物质平衡了过量的细胞渗透压。细胞膨胀后的细胞体积调节涉及通过激活K+通道和/或阴离子通道、KCl共转运或K+/H+交换和Cl-/HCO 3-交换的平行激活来释放离子。细胞收缩后的细胞体积调节涉及通过激活Na+、K+、2Cl(-)共转运、与Cl-/HCO 3-交换平行的Na+/H+交换或Na+通道来积累离子。吸收的Na+被Na+/K+ ATP酶挤出以交换K+。萎缩的细胞通过改变代谢进一步积累有机渗压物质如山梨糖醇和甘油磷酸胆碱,以及单体氨基酸,并通过Na+偶联转运积累肌醇(肌醇)、甜菜碱、牛磺酸和氨基酸。它们在细胞膨胀时释放渗透剂。细胞体积稳态的挑战包括运输,激素,递质和药物。此外,改变。细胞体积参与调节细胞增殖和凋亡性细胞死亡的机制。紊乱的细胞体积调节显著地促成若干病症的病理生理学,诸如肝功能不全、糖尿病酮症酸中毒、高钙血症、纤维化疾病、镰状细胞性贫血和感染。
Survival of human and animal cells requires avoidance of excessive alterations of cell volume. The osmolarity amassed by cellular accumulation of organic substances must be compensated by lowering cytosolic ion concentrations. The Na+/K+ ATPase extrudes Na+ in exchange for K+, which can permeate the cell membrane through K+ channels. K+ exit generates a cell-negative potential difference across the cell membrane, driving the exit of anions such as Cl-. The low cytosolic Cl- concentrations counterbalance the excess cellular osmolarity by organic substances. Cell volume regulation following cell swelling involves releasing ions through activation of K+ channels and/or anion channels, KCI-cotransport, or parallel activation of K+/H+ exchange and Cl-/HCO3- exchange. Cell volume regulation following cell shrinkage involves accumulation of ions through activation of Na+,K+,2CI(-) cotransport, Na+/H+ exchange in parallel to Cl-/HCO3- exchange, or Na+ channels. The Na+ taken up is extruded by the Na+/K+ ATPase in exchange for K+. Shrunken cells further accumulate organic osmolytes such as sorbitol and glycerophosphorylcholine, and monomeric amino acids by altered metabolism and myoinositol (inositol), betaine, taurine, and amino acids by Na+ coupled transport. They release osmolytes during cell swelling. Challenges of cell volume homeostasis include transport, hormones, transmitters, and drugs. Moreover, alterations of. cell volume participate in the machinery regulating cell proliferation and apoptotic cell death. Deranged cell volume regulation significantly contributes to the pathophysiology of several disorders such as liver insufficiency, diabetic ketoacidosis, hypercatabolism, fibrosing disease, sickle cell anemia, and infection.