title: Activation of K(+) channels and increased migration of differentiated intestinal epithelial cells after wounding.
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 Ca(2+) concentration ([Ca(2+)](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 Ca(2+) 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 [Ca(2+)](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 [Ca(2+)](cyt), reduced myosin stress fibers, and inhibited cell migration. Elevation of [Ca(2+)](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 Ca(2+) influx during restitution.
authors.affiliation: Department of Surgery, University of Maryland School of Medicine, 10 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Platoshyn
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Vera A
authors.initials: VA
authors.lastname: Golovina
authors.forename: Jason X-J
authors.initials: JX
authors.lastname: Yuan
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D002118:Calcium / Q000493:pharmacokinetics; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology*; D051662:Kv1.1 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000502:physiology; D024462:Myosin Type II / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D022502:Stress Fibers / Q000378:metabolism; D015534:Trans-Activators; D014162:Transfection; D014945:Wound Healing / Q000502:physiology
chemical_list: D000071616:CDX2 Transcription Factor; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D011073:Polyamines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D015534:Trans-Activators; D051662:Kv1.1 Potassium Channel; D024462:Myosin Type II; D002118:Calcium; D000518:Eflornithine