Pasantes-Morales Herminia
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Mol Pharmacol. 2016 Sep;90(3):358-70. doi: 10.1124/mol.116.104158. Epub 2016 Jun 29.
Volume changes deviating from original cell volume represent a major challenge for cellular homeostasis. Cell volume may be altered either by variations in the external osmolarity or by disturbances in the transmembrane ion gradients that generate an osmotic imbalance. Cells respond to anisotonicity-induced volume changes by active regulatory mechanisms that modify the intracellular/extracellular concentrations of K(+), Cl(-), Na(+), and organic osmolytes in the direction necessary to reestablish the osmotic equilibrium. Corrective osmolyte fluxes permeate across channels that have a relevant role in cell volume regulation. Channels also participate as causal actors in necrotic swelling and apoptotic volume decrease. This is an overview of the types of channels involved in either corrective or pathologic changes in cell volume. The review also underlines the contribution of transient receptor potential (TRP) channels, notably TRPV4, in volume regulation after swelling and describes the role of other TRPs in volume changes linked to apoptosis and necrosis. Lastly we discuss findings showing that multimers derived from LRRC8A (leucine-rich repeat containing 8A) gene are structural components of the volume-regulated Cl(-) channel (VRAC), and we underline the intriguing possibility that different heteromer combinations comprise channels with different intrinsic properties that allow permeation of the heterogenous group of molecules acting as organic osmolytes.
偏离原始细胞体积的体积变化对细胞内稳态构成了重大挑战。细胞体积可能因外部渗透压的变化或跨膜离子梯度的紊乱而改变，后者会导致渗透失衡。细胞通过主动调节机制对非等渗性诱导的体积变化做出反应，这些机制会朝着重新建立渗透平衡所需的方向改变细胞内/外K(+)、Cl(-)、Na(+)和有机渗透物的浓度。纠正性渗透物通量通过在细胞体积调节中起相关作用的通道渗透。通道也作为坏死肿胀和凋亡性体积减小的因果因素参与其中。这是对参与细胞体积纠正性或病理性变化的通道类型的概述。该综述还强调了瞬时受体电位（TRP）通道，特别是TRPV4，在肿胀后体积调节中的作用，并描述了其他TRP在与凋亡和坏死相关的体积变化中的作用。最后，我们讨论了研究结果，这些结果表明源自富含亮氨酸重复序列8A（LRRC8A）基因的多聚体是容积调节性Cl(-)通道（VRAC）的结构成分，并且我们强调了一种有趣的可能性，即不同的异源多聚体组合构成了具有不同内在特性的通道，这些特性允许作为有机渗透物的异质分子组渗透。
