R. Lingameneni et al., Inhibition of voltage-dependent sodium channels by Ro 31-8220, a 'specific' protein kinase C inhibitor, FEBS LETTER, 473(2), 2000, pp. 265-268
We find that several protein kinase C (PKC) inhibitors, previously consider
ed 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 isoquinolinesulf
onamide protein kinase inhibitor), inhibited Na+ channels assessed by sever
al independent criteria: Na+ channel-dependent glutamate release and [H-3]b
atrachotoxinin-A 20-alpha-benzoate binding in rat cortical synaptosomes, ve
ratridine-stimulated Na-22(+) influx in CHO cells expressing rat CNaIIa Na channels and Na+ currents measured in isolated rat dorsal root ganglion ne
urons by whole cell patch-clamp recording. These findings limit the usefuln
ess of the bisindolylmaleimide class PKC inhibitors in excitable cells. (C)
2000 Federation of European Biochemical Societies.