Activation of K+ channels and increased migration of differentiated intestinal epithelial cells after wounding

Jaladanki N. Rao, Oleksandr Platoshyn, Li Li, Xin Guo, Vera A. Golovina, Jason X.J. Yuan, Jian Ying Wang

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Early mucosal restitution occurs by epithelial cell migration to reseal superficial wounds after injury. Differentiated intestinal epithelial cells induced by forced expression of the Cdx2 gene migrate over the wounded edge much faster than undifferentiated parental cells in an in vitro model. This study determined whether these differentiated intestinal epithelial cells exhibit increased migration by altering voltage-gated K+ (Kv) channel expression and cytosolic free Ca2+ concentration ([Ca2+]cyt). Stable Cdx2-transfected IEC-6 cells (IEC-Cdx2L1) with highly differentiated phenotype expressed higher basal levels of Kv1.1 and Kv1.5 mRNAs and proteins than parental IEC-6 cells. Neither IEC-Cdx2L1 cells nor parental IEC-6 cells expressed voltage-dependent Ca2+ channels. The increased expression of Kv channels in differentiated IEC-Cdx2L1 cells was associated with an increase in whole cell K+ currents, membrane hyperpolarization, and a rise in [Ca2+]cyt. The migration rates in differentiated IEC-Cdx2L1 cells were about four times those of parental IEC-6 cells. Inhibition of Kv channel expression by polyamine depletion decreased [Ca2+]cyt, reduced myosin stress fibers, and inhibited cell migration. Elevation of [Ca2+]cyt by ionomycin promoted myosin II stress fiber formation and increased cell migration. These results suggest that increased migration of differentiated intestinal epithelial cells is mediated, at least partially, by increasing Kv channel activity and Ca2+ influx during restitution.

Original languageEnglish (US)
Pages (from-to)C885-C898
JournalAmerican Journal of Physiology - Cell Physiology
Volume282
Issue number4 51-4
StatePublished - Jul 2 2002
Externally publishedYes

Keywords

  • Cdx2 gene
  • Differentiation
  • Intracellular calcium
  • Membrane potential
  • Polyamines
  • Restitution
  • Voltage-gated potassium channels

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Activation of K<sup>+</sup> channels and increased migration of differentiated intestinal epithelial cells after wounding'. Together they form a unique fingerprint.

  • Cite this