科研之友
微信
新浪微博
Facebook
分享链接
摘要
ClC-K2, a member of the ClC family of Cl-channels and transporters, forms the major basolateral Cl-conductance in distal nephron epithelial cells and therefore plays a central role in renal Cl- absorption. However, its regulation remains largely unknown because of the fact that recombinant ClC-K2 has not yet been studied at the single-channel level. In the present study, we investigate the effects of voltage, pH, Cl-, and Ca2+ on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The similar to 10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pH(i)) and extracellular pH (pH(o)) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pH(o) shifts the curve toward negative voltages. In addition, pH(i), pH(o), and extracellular Ca2+ strongly increase activity, mainly because of an increase in the number of active channels with a comparatively minor effect on channel open probability. Furthermore, voltage alters both the number of active channels and their open probability, whereas intracellular Cl- has little influence. We propose that changes in the number of active channels correspond to them entering or leaving an inactivated state, whereas modulation of open probability corresponds to common gating by these channels. We suggest that pH, through the combined effects of pH(i) and pH(o) on ClC-K2, might be a key regulator of NaCl absorption and Cl-/HCO3-exchange in type B intercalated cells.
- 出版日期2016-9
