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Tyrosine kinases modulate K + channel gating in mouse Schwann cells
Author(s) -
Peretz Asher,
Sobko Alexander,
Attali Bernard
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0373m.x
Subject(s) - genistein , gating , tyrosine kinase , chemistry , tyrosine phosphorylation , patch clamp , tyrosine , biophysics , daidzein , kinase , phosphorylation , protein tyrosine phosphatase , endocrinology , biochemistry , biology , signal transduction , receptor
1 The whole‐cell configuration of the patch‐clamp technique and immunoprecipitation experiments were used to investigate the effects of tyrosine kinases on voltage‐dependent K + channel gating in cultured mouse Schwann cells. 2 Genistein, a broad‐spectrum tyrosine kinase inhibitor, markedly reduced the amplitude of a slowly inactivating delayed‐rectifier current ( I K ) and, to a lesser extent, that of a transient K + current ( I A ). Similar results were obtained on I K with another tyrosine kinase inhibitor, herbimycin A. Daidzein, the inactive analogue of genistein, was without effect. 3 Unlike herbimycin A, genistein produced additional effects on I A by profoundly affecting its gating properties. These changes consisted of slower activation kinetics with an increased time to peak, a positive shift in the voltage dependence of activation (by +30 mV), a decrease in the steepness of activation gating (9 mV per e‐fold change) and an acceleration of channel deactivation. 4 The steepness of the steady‐state inactivation was increased by genistein treatment, while the recovery from inactivation was not significantly altered. 5 The action of genistein on voltage‐dependent K + (Kv) currents was accompanied by a decrease in tyrosine phosphorylation of Kv1.4 as well as Kv1.5 and Kv2.1 encoding transient and slowly inactivating delayed‐rectifier K + channel α subunits, respectively. 6 In conclusion, the present study shows that tyrosine kinases markedly affect the amplitude of voltage‐dependent K + currents in Schwann cells and finely tune the gating properties of the transient K + current component I A . These modulations may be functionally relevant in the control of K + channel activity during Schwann cell development and peripheral myelinogenesis.