title: Inhibition of voltage-dependent sodium channels by Ro 31-8220, a 'specific' protein kinase C inhibitor.
abstract: We find that several protein kinase C (PKC) inhibitors, previously considered to be specific, directly inhibit voltage-dependent Na(+) channels at their useful concentrations. Bisindolylmaleimide I (GF 1092037), IX (Ro 31-8220) and V (an inactive analogue), but not H7 (a non-selective isoquinolinesulfonamide protein kinase inhibitor), inhibited Na(+) channels assessed by several independent criteria: Na(+) channel-dependent glutamate release and [(3)H]batrachotoxinin-A 20-alpha-benzoate binding in rat cortical synaptosomes, veratridine-stimulated 22Na(+) influx in CHO cells expressing rat CNaIIa Na(+) channels and Na(+) currents measured in isolated rat dorsal root ganglion neurons by whole cell patch-clamp recording. These findings limit the usefulness of the bisindolylmaleimide class PKC inhibitors in excitable cells.
authors.affiliation: Department of Anesthesiology, Weill Medical College of Cornell University, Box 50, LC-203A, 525 East 68th Street, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lingameneni
authors.forename: T N
authors.initials: TN
authors.lastname: Vysotskaya
authors.forename: D S
authors.initials: DS
authors.lastname: Duch
authors.forename: H C
authors.initials: HC
authors.lastname: Hemmings
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D014701:Veratridine; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C064758:Ro 31-8220