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Kinase‐dependent loss of Na + channel slow‐inactivation in rat CA1 hippocampal pyramidal cell dendrites after brief exposure to convulsants
Author(s) -
Loftis Jordan L.,
King Diana D.,
Colbert Costa M.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02832.x
Subject(s) - chemistry , hippocampal formation , protein kinase a , kinase , convulsant , biophysics , chelerythrine , microbiology and biotechnology , protein kinase inhibitor , extracellular , protein kinase c , neuroscience , biochemistry , biology , receptor
Na + channels in the dendrites of rat CA1 pyramidal neurons display a profound activity‐dependent inactivation, termed slow inactivation, that limits excitability in the dendrites even at low physiological rates of firing. The magnitude of this slow inactivation is powerfully modulated by a protein kinase C‐dependent process. Because activation of kinases is a rapid and common feature of a number of seizure models, we hypothesized that a loss of slow inactivation of Na + channels might exacerbate other changes in excitability. Thus, we observed the effects of a brief (5 min) chemical convulsant treatment on Na + currents and action potentials in hippocampal slices. We found that slow inactivation decreased significantly and remained decreased for at least 30 min after return to control conditions. Pretreatment with either chelerythrine, a protein kinase C inhibitor, or U0126, a mitogen‐activated protein kinase/extracellular signal regulated kinase kinase (MEK) inhibitor, blocked this reduction of slow inactivation. These results demonstrate that a brief period of hyperexcitability leads to a rapid, protein kinase‐dependent loss of slow inactivation of Na + channels that would contribute to and perhaps prolong the hyperexcitable state.