Tyrosine kinases modulate K+ channel gating in mouse Schwann cells

1. The whole-cell configuration of the patch-clamp technique and immunoprec ipitation experiments were used to investigate the effects of tyrosine kina ses 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 pro foundly 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 channe l deactivation. 4. The steepness of the steady-state inactivation was increased by genistei n treatment, while the recovery from inactivation was not significantly alt ered. 5. The action of genistein on voltage-dependent K+ (Kv) currents was accomp anied by a decrease in tyrosine phosphorylation of Kv1.4 as well as Kv1.5 a nd Kv2.1 encoding transient and slowly inactivating delayed-rectifier K+ ch annel alpha subunits, respectively. 6. In conclusion, the present study shows that tyrosine kinases markedly af fect the amplitude of voltage-dependent K+ currents in Schwann cells and fi nely 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.