Extracellular zinc stimulates a calcium-activated chloride conductance through mobilisation of intracellular calcium in renal inner medullary collecting duct cells

Pflugers Arch. 2007 Jan;453(4):487-95. doi: 10.1007/s00424-006-0139-5. Epub 2006 Oct 5.


We have used the perforated patch clamp and fura-2 fluorescence techniques to study the effect of extracellular Zn(2+) on whole-cell Ca(2+)-activated Cl(-) currents (I (CLCA)) in mouse inner medullary collecting duct cells (mIMCD-3). I (CLCA) was spontaneously active in 74% of cells under basal conditions and displayed time and voltage-independent kinetics and an outwardly rectifying current/voltage relationship (I/V). Addition of zinc chloride (10-400 microM) to the bathing solution resulted in a dose-dependent increase in I (CLCA) with little change in Cl(-) selectivity or biophysical characteristics, whereas gadolinium chloride (30 microM) and lanthanum chloride (100 microM) had no significant effect on the whole-cell current. Using fura-2-loaded mIMCD-3 cells, extracellular Zn(2+) (400 microM) stimulated an increase in intracellular Ca(2+) to an elevated plateau. The Zn(2+)-stimulated [Ca(2+)](i) increase was inhibited by thapsigargin (200 nM), the IP(3) receptor antagonist 2-aminoethoxydiphenyl borate (10 microM) and removal of bath Ca(2+). Pre-exposure to Zn(2+) (400 microM) markedly attenuated the ATP (100 microM)-stimulated [Ca(2+)](i) increase. These data are consistent with the hypothesis that extracellular Zn(2+) stimulates an increase in [Ca(2+)](i) by a release of calcium from thapsigargin/IP(3) sensitive stores. A possible physiological role for a divalent metal ion receptor, distinct from the extracellular Ca(2+)-sensing receptor, in IMCD cells is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron Compounds / pharmacology
  • Calcium / metabolism*
  • Cells, Cultured
  • Chloride Channels / metabolism
  • Chloride Channels / physiology*
  • Chlorides / pharmacology
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Fluorometry
  • Kidney Medulla / cytology
  • Kidney Medulla / drug effects*
  • Kidney Medulla / metabolism
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / drug effects*
  • Kidney Tubules, Collecting / metabolism
  • Membrane Potentials / drug effects
  • Mice
  • Patch-Clamp Techniques
  • Thapsigargin / pharmacology
  • Zinc / pharmacology*
  • Zinc Compounds / pharmacology


  • Boron Compounds
  • Chloride Channels
  • Chlorides
  • Zinc Compounds
  • Thapsigargin
  • zinc chloride
  • 2-aminoethoxydiphenyl borate
  • Zinc
  • Calcium