Authors: Zhanfeng Jia Yueqin Jia Boyi Liu Zhiying Zhao Qingzhong Jia Huiling Liang Hailin Zhang
Publish Date: 2008/01/29
Volume: 456, Issue: 5, Pages: 857-866
Abstract
Voltagegated sodium channels play a crucial role in the initiation and propagation of neuronal action potentials Genistein an isoflavone phytoestrogen has long been used as a broadspectrum inhibitor of protein tyrosine kinases PTK In addition genisteininduced modulation of ion channels has been described previously in the literature In this study we investigated the effect of genistein on voltagegated sodium channels in rat superior cervical ganglia SCG neurons The results show that genistein inhibits Na+ currents in a concentrationdependent manner with a concentration of halfmaximal effect IC50 at 91 ± 09 μM Genistein positively shifted the voltage dependence of activation but did not affect inactivation of the Na+ current The inactive genistein analog daidzein also inhibited Na+ currents but was less effective than genistein The IC50 for daidzeininduced inhibition was 207 ± 01 μM Vanadate an inhibitor of protein tyrosine phosphatases partially but significantly reversed genisteininduced inhibition of Na+ currents Other protein tyrosine kinase antagonists such as tyrphostin 23 an erbstatin analog and PP2 all had small but significant inhibitory effects on Na+ currents Among all active and inactive tyrosine kinase inhibitors tested genistein was the most potent inhibitor of Na+ currents These results suggest that genistein inhibits Na+ currents in rat SCG neurons through two distinct mechanisms protein tyrosine kinaseindependent and protein tyrosine kinasedependent mechanisms Furthermore the Src kinase family may be involved in the basal phosphorylation of the Na+ channel
Keywords: