title: Subsets of ATP-sensitive potassium channel (KATP) inhibitors increase gap junctional intercellular communication in metastatic cancer cell lines independent of SUR expression.
abstract: Gap junctional intercellular communication (GJIC) regulates cellular homeostasis by propagating signaling molecules, exchanging cellular metabolites, and coupling electrical signals. In cancer, cells exhibit altered rates of GJIC which may play a role in neoplastic progression. K(ATP) channels help maintain membrane polarity and linkages between K(ATP) channel activity and rates of GJIC have been established. The mechanistic relationship has not been fully elucidated. We report the effects of treatment with multiple K(ATP) antagonist compounds on GJIC in metastatic cell lines demonstrating an increase in communication rates following treatment with compounds possessing specificities towards the SUR2 subunit of K(ATP). These effects remained consistent using cell lines with different expression levels of SUR1 and SUR2, suggesting possible off target effects on GJIC by these compounds.
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Thomas M
authors: TM
authors: Bodenstine
authors: Kedar S
authors: KS
authors: Vaidya
authors: Aimen
authors: A
authors: Ismail
authors: Benjamin H
authors: BH
authors: Beck
authors: Anne R
authors: AR
authors: Diers
authors: Mick D
authors: MD
authors: Edmonds
authors: Gina T
authors: GT
authors: Kirsammer
authors: Aimee
authors: A
authors: Landar
authors: Danny R
authors: DR
authors: Welch
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor / Q000473:pathology; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D054086:KATP Channels / Q000037:antagonists & inhibitors*; D056892:Mediator Complex / Q000378:metabolism*; D009362:Neoplasm Metastasis; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D064233:Sulfonylurea Receptors
chemical_list: C577507:ABCC8 protein, human; C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; C492159:MED23 protein, human; D056892:Mediator Complex; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors