Transient suppression of gap junctional intercellular communication after exposure to 100-nanosecond pulsed electric fields

• Published in: Bioelectrochemistry (Amsterdam, Netherlands) Vol. 112; pp. 33 - 46
• Main Authors: Steuer, Anna, Schmidt, Anke, Labohá, Petra, Babica, Pavel, Kolb, Juergen F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2016
• Subjects: Actin; Actins - metabolism; Animals; Cell Communication; Cell Line; Cell Survival; Connexin 43; Connexin 43 - genetics; Connexin 43 - metabolism; Cx43; Electricity; Enzyme Activation; Gap Junctions - metabolism; Gene Expression Regulation; GJIC; Male; MAP kinase; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; nsPEF; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Rats; Time Factors; Zonula Occludens-1 Protein - metabolism; MAP kinase; Connexin 43; Cx43; GJIC; Actin; nsPEF
• ISSN: 1567-5394; 1878-562X
• DOI: 10.1016/j.bioelechem.2016.07.003

Gap junctional intercellular communication (GJIC) is an important mechanism that is involved and affected in many diseases and injuries. So far, the effect of nanosecond pulsed electric fields (nsPEFs) on the communication between cells was not investigated. An in vitro approach is presented with rat liver epithelial WB-F344 cells grown and exposed in a monolayer. In order to observe sub-lethal effects, cells were exposed to pulsed electric fields with a duration of 100ns and amplitudes between 10 and 20kV/cm. GJIC strongly decreased within 15min after treatment but recovered within 24h. Gene expression of Cx43 was significantly decreased and associated with a reduced total amount of Cx43 protein. In addition, MAP kinases p38 and Erk1/2, involved in Cx43 phosphorylation, were activated and Cx43 became hyperphosphorylated. Immunofluorescent staining of Cx43 displayed the disassembly of gap junctions. Further, a reorganization of the actin cytoskeleton was observed whereas tight junction protein ZO-1 was not significantly affected. All effects were field- and time-dependent and most pronounced within 30 to 60min after treatment. A better understanding of a possible manipulation of GJIC by nsPEFs might eventually offer a possibility to develop and improve treatments. [Display omitted] •NsPEFs inhibit gap junctional intercellular communication in WB-F344 cells.•Inhibition was transient and time- and field strength-dependent.•The mechanism probably relies on the activation of MAPK.•Gene and protein expression of Cx43 were also down-regulated.