Inhibition of voltage‐dependent sodium channels by Ro 31‐8220, a ‘specific’ protein kinase C inhibitor

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Protein kinase inhibitor;Protein kinase C;Glutamate release;Na+ channel;Synaptosome;Dorsal root ganglion neuron