TrkB activation by brain-derived neurotrophic factor inhibits the G protein-gated inward rectifier Kir3 by tyrosine phosphorylation of the channel.

ABSTRACT: G protein-activated inwardly rectifying potassium channels (Kir3) are widely expressed throughout the brain, and regulation of their activity modifies neuronal excitability and synaptic transmission. In this study, we show that the neurotrophin brain-derived neurotrophic factor (BDNF), through activation of TrkB receptors, strongly inhibited the basal activity of Kir3. This inhibition was subunit dependent as functional homomeric channels of either Kir3.1 or Kir3.4 were significantly inhibited, whereas homomeric channels composed of Kir3.2 were insensitive. The general tyrosine kinase inhibitors genistein, Gö 6976, and K252a but not the serine/threonine kinase inhibitor staurosporine blocked the BDNF-induced inhibition of the channel. BDNF was also found to directly stimulate channel phosp

SUBMITTER: Rogalski SL 

PROVIDER: S-EPMC1276699 | biostudies-literature | 2000 Aug

REPOSITORIES: biostudies-literature