title: Non-hydrolyzable analog of GTP induces activity of Na+ channels via disassembly of cortical actin cytoskeleton.
abstract: The role of G proteins in regulation of non-voltage-gated Na+ channels in human myeloid leukemia K562 cells was studied by inside-out patch-clamp method. Na+ channels were activated by non-hydrolyzable analog of guanosine triphosphate (GTP), GTPgammaS, known to activate both heterotrimeric and small G proteins. Channel activity was not affected by aluminum fluoride that indiscriminately activates heterotrimeric G proteins. The effect of GTPgammaS was prevented by phalloidin and by G-actin, both interfering with actin disassembly, which indicates that GTPgammaS-induced channel activation was likely due to microfilament disruption. GTPgammaS-activated channels were inactivated by polymerizing actin. These data show, for the first time, that small G proteins can regulate Na+ channels, and an intracellular mechanism mediating their effect involves actin cytoskeleton rearrangements.
authors.affiliation: Institute of Cytology RAS, 4 Tikhoretsky Ave., 194064, St. Petersburg, Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Shumilina
authors.forename: Sofia Yu
authors.initials: SY
authors.lastname: Khaitlina
authors.forename: Elena A
authors.initials: EA
authors.lastname: Morachevskaya
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Negulyaev
mesh_terms: D000199:Actins / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D015222:Sodium Channels; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins