Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration

Jian Ying Wang, Jian Wang, Vera A. Golovina, L. I. Li, Oleksandr Platoshyn, Jason Xiao Jian Yuan

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K+ channels (Kv) controls membrane potential (E(m)) that regulates cytoplasmic free Ca2+ concentration ([Ca2+](cyt)) by governing the driving force for Ca2+ influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K+ channel gene expression, E(m), and [Ca2+](cyt) in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, α- difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca2+ channels, the depolarized E(m) in DFMO-treated cells decreased [Ca2+](cyt) as a result of reduced driving force for Ca2+ influx through capacitative Ca2+ entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E(m), and [Ca2+](cyt) but also restored cell migration to normal. Removal of extracellular Ca2+ or blockade of Kv channels (by 4- aminopyridine, 1-5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca2+](cyt) by increasing the driving force (the electrochemical gradient) for Ca2+ influx and thus stimulates cell migration.

Original languageEnglish (US)
Pages (from-to)C303-C314
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number2 47-2
DOIs
StatePublished - 2000

Keywords

  • Intestinal epithelial cells
  • Intracellular calcium
  • Membrane potential
  • Polyamines
  • Voltage-gated potassium channels

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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