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Inhibition of voltage‐dependent sodium channels by Ro 31‐8220, a ‘specific’ protein kinase C inhibitor
Author(s) -
Lingameneni Ratnakumari,
Vysotskaya Tanya N.,
Duch Daniel S.,
Hemmings Hugh C.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01532-5
Subject(s) - bisindolylmaleimide , protein kinase c , dorsal root ganglion , sodium channel , veratridine , patch clamp , protein kinase a , biophysics , protein kinase inhibitor , chemistry , microbiology and biotechnology , biology , endocrinology , medicine , biochemistry , sodium , kinase , anatomy , receptor , dorsum , organic chemistry
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‐α‐benzoate binding in rat cortical synaptosomes, veratridine‐stimulated 22 Na + 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.