title: Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps.
abstract: Transepithelial potential (TEP) is the voltage across a polarized epithelium. In epithelia that have active transport functions, the force for transmembrane flux of an ion is dictated by the electrochemical gradient in which TEP plays an essential role. In epithelial injury, disruption of the epithelial barrier collapses the TEP at the wound edge, resulting in the establishment of an endogenous wound electric field (∼100 mV/mm) that is directed towards the center of the wound. This endogenous electric field is implicated to enhance wound healing by guiding cell migration. We thus seek techniques to enhance the TEP, which may increase the wound electric fields and enhance wound healing. We report a novel technique, termed synchronization modulation (SM) using a train of electric pulses to synchronize the Na/K pump activity, and then modulating the pumping cycles to increase the efficiency of the Na/K pumps. Kidney epithelial monolayers (MDCK cells) maintain a stable TEP and transepithelial resistance (TER). SM significantly increased TEP over four fold. Either ouabain or digoxin, which block Na/K pump, abolished SM-induced TEP increases. In addition to the pump activity, basolateral distribution of Na/K pumps is essential for an increase in TEP. Our study for the first time developed an electrical approach to significantly increase the TEP. This technique targeting the Na/K pump may be used to modulate TEP, and may have implication in wound healing and in diseases where TEP needs to be modulated.
authors.affiliation: Institute for Regenerative Cures, Departments of Dermatology and Ophthalmology, University of California Davis, Davis, California, United States of America.
authors.forename: Vu
authors.initials: V
authors.lastname: Tran
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.forename: Hanqing
authors.initials: H
authors.lastname: Li
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lee
authors.forename: Michelle
authors.initials: M
authors.lastname: So
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D061985:Madin Darby Canine Kidney Cells; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D010042:Ouabain / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology; D014947:Wounds and Injuries / Q000473:pathology / Q000628:therapy
chemical_list: D004791:Enzyme Inhibitors; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase