GABA-B controls persistent Na+ current and coupled Na+-activated K+ current

Ping Li, Richard Stewart, Alice Butler, Ana Laura Gonzalez-Cota, Steve Harmon, Lawrence Salkoff

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The GABA-B receptor is densely expressed throughout the brain and has been implicated in many CNS functions and disorders, including addiction, epilepsy, spasticity, schizophrenia, anxiety, cognitive deficits, and depression, as well as various aspects of nervous system development. How one GABA-B receptor is involved in so many aspects of CNS function remains unanswered. Activation of GABA-B receptors is normally thought to produce inhibitory responses in the nervous system, but puzzling contradictory responses exist. Here we report that in rat mitral cells of the olfactory bulb, GABA-B receptor activation inhibits both the persistent sodium current (INaP) and the sodium-activated potassium current (IKNa), which is coupled to it. We find that the primary effect of GABA-B activation is to inhibit INaP, which has the secondary effect of inhibiting IKNa because of its dependence on persistent sodium entry for activation. This can have either a net excitatory or inhibitory effect depending on the balance of INaP/IKNa currents in neurons. In the olfactory bulb, the cell bodies of mitral cells are densely packed with sodium-activated potassium channels. These channels produce a large IKNa which, if constitutively active, would shunt any synaptic potentials traversing the soma before reaching the spike initiation zone. However, GABA-B receptor activation might have the net effect of reducing the IKNa blocking effect, thus enhancing the effectiveness of synaptic potentials.

Original languageEnglish
Article numbere0114-17.2017
JournaleNeuro
Volume4
Issue number3
DOIs
StatePublished - 2017

Keywords

  • Baclofen
  • GABA-B
  • Mitral cell
  • Olfactory bulb
  • Persistent sodium current
  • Potassium channel
  • SLO2
  • Slick

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