title: Connexin37 forms high conductance gap junction channels with subconductance state activity and selective dye and ionic permeabilities.
abstract: Gap junctions are thought to mediate the direct intercellular coupling of adjacent cells by the open-closed gating of an aqueous pore permeable to ions and molecules of up to 1 kDa or 10-14 A in diameter. We symmetrically altered the ionic composition or asymmetrically added 6-carboxyfluorescein (6-CF, M(r) = 376), a fluorescent tracer, to pairs of connexin37-transfected mouse neuro2A cells to examine the ionic and dye permeability of human connexin37 channels. We demonstrate that the 300-pS channel formed by connexin37 has an effective relative anion/cation permeability ratio of 0.43, directly converts to at least one intermediate (63 pS) subconductance state, and that 6-CF dye transfer is accompanied by a 24% decrease in unitary channel conductance. These observations favor a new interpretation of the gap junction pore consistent with direct ion-channel interactions or electrostatic charge effects common to more conventional multistate ion channels. These results have distinct implications about the different forms of intercellular signaling (cationic, ionic, and/or biochemical) that can occur depending on the expression and conformation of the connexin channel proteins.
authors.affiliation: Department of Pharmacology, SUNY Health Science Center at Syracuse 13210.
authors.forename: R D
authors.initials: RD
authors.lastname: Veenstra
authors.forename: H Z
authors.initials: HZ
authors.lastname: Wang
authors.forename: E C
authors.initials: EC
authors.lastname: Beyer
authors.forename: S V
authors.initials: SV
authors.lastname: Ramanan
authors.forename: P R
authors.initials: PR
authors.lastname: Brink
mesh_terms: D000818:Animals; D002460:Cell Line; D017630:Connexins / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000502:physiology*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials; D051379:Mice; D008954:Models, Biological; D009447:Neuroblastoma; D011336:Probability; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000097006:Gap Junction alpha-4 Protein
chemical_list: D017630:Connexins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007473:Ion Channels; D000097006:Gap Junction alpha-4 Protein; C024098:6-carboxyfluorescein