Inhibition of voltage-dependent sodium channels by Ro 31-8220, a ‘specific’ protein kinase C inhibitor1
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Add time:09/01/2019 Source:sciencedirect.com
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 [3H]batrachotoxinin-A 20-α-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.
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