Kidd J F, Thorn P
Department of Pharmacology, University of Cambridge, United Kingdom.
Annu Rev Physiol. 2000;62:493-513. doi: 10.1146/annurev.physiol.62.1.493.
Molecular and functional evidence indicates that a variety of Ca(2+)-dependent chloride (Cl(Ca)) channels are involved in fluid secretion from secretory epithelial cells in different tissues and species. Most Cl(Ca) channels so far characterized have an I- permeability greater than Cl-, and most are sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Whole-cell Cl(Ca) currents show outward rectification. Single-channel current voltage relationships are linear with conductances ranging from 2 to 30 pS. Some Cl(Ca) channels are blocked by Ca(2+)-calmodulin-dependent protein kinase (CAMKII) inhibitors. Others, such as the Cl(Ca) channels of parotid and submandibular acinar cells, appear to be directly regulated by Ca2+. In native cells, the Cl(Ca) channels are located on the apical plasma membrane and activated by localized mechanisms of Ca2+ release. This positioning allows the Cl(Ca) channel to respond specifically to localized Ca2+ signals that do not invade other regions of the cell. The Cl(Ca) follows the rising phase of the Ca2+ signal, but in the falling phase hysteresis occurs where the Cl(Ca) current decays more rapidly than the underlying Ca2+. The future elucidation of the identity and mechanisms of regulation of Cl(Ca) channels will be critical to our understanding of stimulus-secretion coupling.
分子和功能证据表明，多种钙依赖性氯（Cl(Ca)）通道参与了不同组织和物种中分泌上皮细胞的液体分泌。迄今为止所鉴定的大多数Cl(Ca)通道对碘的通透性大于对氯的通透性，并且大多数对4,4'-二异硫氰基芪-2,2'-二磺酸（DIDS）敏感。全细胞Cl(Ca)电流呈现外向整流。单通道电流-电压关系呈线性，电导范围为2至30 pS。一些Cl(Ca)通道被钙-钙调蛋白依赖性蛋白激酶（CAMKII）抑制剂阻断。其他通道，如腮腺和下颌下腺腺泡细胞的Cl(Ca)通道，似乎直接受Ca2+调节。在天然细胞中，Cl(Ca)通道位于顶端质膜上，并由局部Ca2+释放机制激活。这种定位使Cl(Ca)通道能够特异性地响应不侵入细胞其他区域的局部Ca2+信号。Cl(Ca)跟随Ca2+信号的上升阶段，但在下降阶段会出现滞后现象，即Cl(Ca)电流的衰减比潜在的Ca2+更快。未来对Cl(Ca)通道的身份和调节机制的阐明对于我们理解刺激-分泌偶联至关重要。
