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Department of Anesthesiology

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Inhibition of voltage-dependent sodium channels by Ro 31-8220, a 'specific' protein kinase C inhibitor.

TitleInhibition of voltage-dependent sodium channels by Ro 31-8220, a 'specific' protein kinase C inhibitor.
Publication TypeJournal Article
Year of Publication2000
AuthorsLingameneni R, Vysotskaya TN, Duch DS, Hemmings HC
JournalFEBS Lett
Date Published2000 May 12
KeywordsAnimals, Binding, Competitive, Cerebral Cortex, CHO Cells, Cricetinae, Dose-Response Relationship, Drug, Enzyme Inhibitors, Ganglia, Spinal, Glutamic Acid, Indoles, Maleimides, Membrane Potentials, Neurons, Patch-Clamp Techniques, Protein Kinase C, Rats, Rats, Sprague-Dawley, Sodium Channel Blockers, Synaptosomes, Veratridine

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.

Alternate JournalFEBS Lett.
PubMed ID10812087
Grant ListGM 58055 / GM / NIGMS NIH HHS / United States