Biophysical and pharmacological characterization of chloride currents in human astrocytoma cells

Am J Physiol. 1996 May;270(5 Pt 1):C1511-21. doi: 10.1152/ajpcell.1996.270.5.C1511.


Expression of voltage-activated ion channels was studied in primary cultures from seven freshly resected human primary brain tumors and in an established human astrocytoma cell line, STTG1. Astrocytoma cells consistently expressed voltage-dependent outwardly rectifying currents. Currents activated at potentials > 45 mV and showed outward transients on termination of voltage steps. Currents reversed at the Cl equilibrium potential, suggesting that they were largely carried by Cl-. Altering extracellular K- or Na+ concentration did not alter currents; neither did replacement of intracellular K+ by Cs+ or intracellular Na+ by N-methyl-D-glucosamine. Anion-substitution experiments suggest the following permeability sequence, determined from shifts in tail current reversal potential: I- > NO3- > Br- > Cl- > acetate > isethionate > F- > glutamate. Currents were sensitive to the Cl- channel blockers chlorotoxin, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and 4,4'-dinitrostilbene-2,2' disulfonic acid (DNDS), with chlorotoxin being most effective, yielding > 80% block at 590 nM. DIDS (100 microM) and DNDS (100 microM) reduced currents by 33.5 and 38.2%, respectively. Currents were also sensitive to Zn2+ (100 microM, 47% block) and Cd2- (25 microM, 42% block). Reducing extracellular Ca2+ concentration decreased outward currents by 58% and almost completely eliminated transients, suggesting that Cl- currents are Ca2+ dependent. Cl channel block resulted in altered cell proliferation as determined by [3H]thymidine incorporation, suggesting that these channels may be involved in astrocytoma growth control.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Astrocytoma / pathology
  • Astrocytoma / physiopathology*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / physiopathology*
  • Cell Division
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / metabolism
  • Chlorides / physiology*
  • Electric Conductivity
  • Humans
  • Scorpion Venoms / pharmacology
  • Stilbenes / pharmacology
  • Tumor Cells, Cultured


  • Chloride Channels
  • Chlorides
  • Scorpion Venoms
  • Stilbenes
  • Chlorotoxin
  • 4,4'-dinitro-2,2'-stilbenedisulfonic acid
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid