Activation of epidermal growth factor receptor inhibits KCNQ2/3 current through two distinct pathways: membrane PtdIns(4,5)P2 hydrolysis and channel phosphorylation.

Journal Article (Journal Article)

KCNQ2/3 currents are the molecular basis of the neuronal M currents that play a critical role in neuron excitability. Many neurotransmitters modulate M/KCNQ currents through their G-protein-coupled receptors. Membrane PtdIns(4,5)P2 hydrolysis and channel phosphorylation are two mechanisms that have been proposed for modulation of KCNQ2/3 currents. In this study, we studied regulation of KCNQ2/3 currents by the epidermal growth factor (EGF) receptor, a member of another family of membrane receptors, receptor tyrosine kinases. We demonstrate here that EGF induces biphasic inhibition of KCNQ2/3 currents in human embryonic kidney 293 cells and in rat superior cervical ganglia neurons, an initial fast inhibition and a later slow inhibition. Additional studies indicate that the early and late inhibitions resulted from PtdIns(4,5)P2 hydrolysis and tyrosine phosphorylation, respectively. We further demonstrate that these two processes are mutually dependent. This study indicates that EGF is a potent modulator of M/KCNQ currents and provides a new dimension to the understanding of the modulation of these channels.

Full Text

Duke Authors

Cited Authors

  • Jia, Q; Jia, Z; Zhao, Z; Liu, B; Liang, H; Zhang, H

Published Date

  • March 7, 2007

Published In

Volume / Issue

  • 27 / 10

Start / End Page

  • 2503 - 2512

PubMed ID

  • 17344388

Pubmed Central ID

  • PMC6672518

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.2911-06.2007


  • eng

Conference Location

  • United States