Tyrosine kinases modulate K+ channel gating in mouse Schwann cells

Asher Peretz, Alexander Sobko, Bernard Attali

Research output: Contribution to journalArticlepeer-review

Abstract

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. 8. 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.

Original languageEnglish
Pages (from-to)373-384
Number of pages12
JournalJournal of Physiology
Volume519
Issue number2
DOIs
StatePublished - 1 Sep 1999
Externally publishedYes

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