Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Jožef Stefan Institute, Ljubljana, Slovenia.
Jožef Stefan Institute, Ljubljana, Slovenia.
Biophys J. 2019 Jan 8;116(1):151-164. doi: 10.1016/j.bpj.2018.11.3130. Epub 2018 Dec 4.
A red blood cell (RBC) performs its function of adequately carrying respiratory gases in blood by its volume being ∼60% of that of a sphere with the same membrane area. For this purpose, human and most other vertebrate RBCs regulate their content of potassium (K) and sodium (Na) ions. The focus considered here is on K efflux through calcium-ion (Ca)-activated Gárdos channels. These channels open under conditions that allow Ca to enter RBCs through Piezo1 mechanosensitive cation-permeable channels. It is postulated that the fraction of open Piezo1 channels depends on the RBC shape as a result of the curvature-dependent Piezo1-bilayer membrane interaction. The consequences of this postulate are studied by introducing a simple model of RBC osmotic behavior supplemented by the dependence of RBC membrane K permeability on the reduced volume (i.e., the ratio of cell volume to its maximal possible volume) of RBC discoid shapes. It is assumed that because of its intrinsic curvature and strong interaction with the surrounding membrane, Piezo1 tends to concentrate in the dimple regions of these shapes, and the fraction of open Piezo1 channels depends on the membrane curvature in that region. It is shown that the properties of the described model can provide the basis for the formation of the negative feedback loop that interrelates cell volume and its content of potassium ions. The model predicts the relation, valid for each cell in an RBC population, between RBC volume and membrane area, thus explaining the large value of the measured membrane area versus the volume correlation coefficient. The mechanism proposed here for RBC volume regulation is in accord with the loss of this correlation in RBCs of Piezo1 knockout mice.
红细胞（RBC）通过其体积约为具有相同膜面积的球体的 60%，从而充分发挥其在血液中携带呼吸气体的功能。为此，人和大多数其他脊椎动物 RBC 调节其钾（K）和钠（Na）离子的含量。这里关注的焦点是通过钙激活的 Gárdos 通道的 K 外流。这些通道在允许 Ca 通过 Piezo1 机械敏感阳离子渗透性通道进入 RBC 的条件下打开。据推测，由于 RBC 形状的曲率依赖性 Piezo1-双层膜相互作用，开放的 Piezo1 通道的分数取决于 RBC 形状。通过引入补充 RBC 膜 K 渗透性对 RBC 盘状形状的减小体积（即细胞体积与其最大可能体积之比）的依赖性的 RBC 渗透行为的简单模型，研究了这一假设的后果。假设由于其内在曲率和与周围膜的强烈相互作用，Piezo1 倾向于集中在这些形状的凹陷区域，并且开放的 Piezo1 通道的分数取决于该区域的膜曲率。结果表明，所描述模型的特性可以为细胞体积与其钾离子含量之间的负反馈循环的形成提供基础。该模型预测了描述的模型的特性可以为细胞体积与其钾离子含量之间的负反馈循环的形成提供基础。该模型预测了描述的模型的特性可以为细胞体积与其钾离子含量之间的负反馈循环的形成提供基础。该模型预测了对于 RBC 群体中的每个细胞都有效的 RBC 体积与膜面积之间的关系，从而解释了测量的膜面积与体积相关系数之间的大值。这里提出的用于 RBC 体积调节的机制与 Piezo1 敲除小鼠 RBC 中这种相关性的丧失一致。
