title: Intracellular spermine prevents acid-induced uncoupling of Cx43 gap junction channels.
abstract: Polyamines (PAs), such as spermine and spermidine, modulate the activity of numerous receptors and channels in the central nervous system (CNS) and are stored in glial cells; however, little attention has been paid to their role in the regulation of connexin (Cx)-based gap junction channels. We have previously shown that PAs facilitate diffusion of Lucifer Yellow through astrocytic gap junctions in acute brain slices; therefore, we hypothesized that spermine can regulate Cx43-mediated (as the most abundant Cx in astrocytes) gap junctional communication. We used electrophysiological patch-clamp recording from paired Novikoff cells endogenously expressing Cx43 and HeLaCx43-EGFP transfectants to study pH-dependent modulation of cell-cell coupling in the presence or absence of PAs. Our results showed (i) a higher increase in gap junctional communication at higher concentrations of cytoplasmic spermine, and (ii) that spermine prevented uncoupling of gap junctions at low intracellular pH. Taken together, we conclude that spermine enhances Cx43-mediated gap junctional communication and may preserve neuronal excitability during ischemia and trauma when pH in the brain acidifies. We, therefore, suggest a new role of spermine in the regulation of a Cx43-based network under (patho)physiological conditions.
authors.affiliation: Departments of aPhysiology bBiochemistry, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico cDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Yeshiva University, New York, New York, USA.
authors.forename: Serguei N
authors.initials: SN
authors.lastname: Skatchkov
authors.forename: Feliksas F
authors.initials: FF
authors.lastname: Bukauskas
authors.forename: Jan
authors.initials: J
authors.lastname: Benedikt
authors.forename: Mikhail
authors.initials: M
authors.lastname: Inyushin
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Kucheryavykh
mesh_terms: D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism*; D004553:Electric Conductivity; D017629:Gap Junctions / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013096:Spermine / Q000494:pharmacology*
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D013096:Spermine