Regulation of apical Cl- conductance and basolateral K+ conductances by phorbol esters in HT-29cl.19A cells

Am J Physiol. 1992 Oct;263(4 Pt 1):C759-66. doi: 10.1152/ajpcell.1992.263.4.C759.

Abstract

The effect of phorbol esters [4 beta-phorbol 12,13-dibutyrate (PDB) and phorbol 12-myristate 13-acetate (PMA)] on potential differences and resistances was studied with the conventional microelectrode technique applied to confluent filter-grown monolayers of the human colon carcinoma cell line HT-29cl.19A. Phorbol esters (PDB or PMA from 10(-7) to 10(-6) M) evoked 1) a transient increase in the transepithelial potential difference (peak value 3.5 +/- 0.5 mV), 2) a depolarization of the cell potential by 23 +/- 2 mV at the peak of the transepithelial potential change and a continued decrease during the decline of the transepithelial potential, and 3) a decrease of the fractional resistance of the apical membrane consisting of two phases, a relative rapid one (time constant 1.2 +/- 0.2 min) and a much slower further decrease during the second phase (time constant 34 +/- 1 min). Ion replacements and electrical circuit analyses indicate that PDB activates an apical Cl- conductance and slowly inhibits the basal K+ conductance of the basolateral membrane. PDB reduced the transepithelial response to forskolin due to inhibition of the basal K+ conductance. The Ca2+ ionophore ionomycin accelerated that effect of PDB. Staurosporine inhibited the effects of PDB, suggesting that the PDB effects are mediated via activation of a protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / physiology
  • Carcinoma / pathology
  • Carcinoma / physiopathology*
  • Cell Membrane / physiology
  • Chlorides / physiology*
  • Colforsin / pharmacology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / physiopathology*
  • Electric Conductivity
  • Humans
  • Phorbol 12,13-Dibutyrate / pharmacology*
  • Potassium / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Chlorides
  • Colforsin
  • Phorbol 12,13-Dibutyrate
  • Tetradecanoylphorbol Acetate
  • Potassium
  • Calcium