Correlation Engine 2.0
Clear Search sequence regions

  • anion transport proteins (2)
  • b cells (1)
  • Ca 2 (2)
  • calcium (2)
  • cells (1)
  • Cl 2 (1)
  • ClC K2 (5)
  • Clcnkb protein (1)
  • hydrogen ion (1)
  • intracellular (2)
  • ion channel (1)
  • male (1)
  • membrane cells (2)
  • mice (1)
  • minor (1)
  • native (2)
  • nephron (3)
  • sodium (2)
  • Sizes of these terms reflect their relevance to your search.

    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 Ca(2+) on native ClC-K2 in the basolateral membrane of intercalated cells from the mouse connecting tubule. The ∼10-pS channel shows a steep voltage dependence such that channel activity increases with membrane depolarization. Intracellular pH (pHi) and extracellular pH (pHo) differentially modulate the voltage dependence curve: alkaline pHi flattens the curve by causing an increase in activity at negative voltages, whereas alkaline pHo shifts the curve toward negative voltages. In addition, pHi, pHo, and extracellular Ca(2+) 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 pHi and pHo on ClC-K2, might be a key regulator of NaCl absorption and Cl(-)/HCO3 (-) exchange in type B intercalated cells. © 2016 Pinelli et al.


    Laurent Pinelli, Antoine Nissant, Aurélie Edwards, Stéphane Lourdel, Jacques Teulon, Marc Paulais. Dual regulation of the native ClC-K2 chloride channel in the distal nephron by voltage and pH. The Journal of general physiology. 2016 Sep;148(3):213-26

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 27574292

    View Full Text