Minton A P, Colclasure G C, Parker J C
Laboratory of Biochemical Pharmacology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10504-6. doi: 10.1073/pnas.89.21.10504.
A simple model is proposed to account for large increases in transporter-mediated ion flux across cell membranes that are elicited by small fractional changes of cell volume. The model is based upon the concept that, as a result of large excluded volume effects in cytoplasm (macromolecular crowding), the tendency of soluble macromolecules to associate with membrane proteins is much more sensitive to changes in cell water content than expected on the basis of simple considerations of mass action. The model postulates that an ion transporter may exist in either an active dephosphorylated state or an inactive phosphorylated state and that the steady-state activity of the transporter reflects a balance between the rates of phosphatase-catalyzed activation and kinase-catalyzed inactivation. Cell swelling results in the inhibition of kinase relative to phosphatase activity, thereby increasing the steady-state concentration of the active form of the transporter. Calculated volume-dependent stimulation of ion flux is comparable to that observed experimentally.
提出了一个简单模型，以解释细胞体积的微小分数变化引起的跨细胞膜转运体介导的离子通量大幅增加的现象。该模型基于这样一个概念，即由于细胞质中存在大量的排阻体积效应（大分子拥挤），可溶性大分子与膜蛋白结合的倾向对细胞含水量变化的敏感度，比基于简单质量作用考虑所预期的要高得多。该模型假定离子转运体可能以活性去磷酸化状态或非活性磷酸化状态存在，且转运体的稳态活性反映了磷酸酶催化的激活速率和激酶催化的失活速率之间的平衡。细胞肿胀导致激酶活性相对于磷酸酶活性受到抑制，从而增加了转运体活性形式的稳态浓度。计算得出的离子通量随体积变化的刺激与实验观察结果相当。
