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 Yuan

Research output: Contribution to journalArticle

79 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number2 47-2
StatePublished - 2000
Externally publishedYes

Fingerprint

Polyamines
Cell Movement
Epithelial Cells
Spermidine
Membranes
Eflornithine
Voltage-Gated Potassium Channels
4-Aminopyridine
Putrescine
Spermine
Depolarization
Gene expression
Membrane Potentials
Restoration
Gastrointestinal Tract
Cells
Gene Expression
Electric potential

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration. / Wang, Jian Ying; Wang, Jian; Golovina, Vera A.; Li, L. I.; Platoshyn, Oleksandr; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 278, No. 2 47-2, 2000.

Research output: Contribution to journalArticle

Wang, Jian Ying ; Wang, Jian ; Golovina, Vera A. ; Li, L. I. ; Platoshyn, Oleksandr ; Yuan, Jason. / Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 278, No. 2 47-2.
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AU - Yuan, Jason

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AB - 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.

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