GABA-B Controls Persistent Na + Current and Coupled Na + -Activated K + Current

• Published in: eNeuro Vol. 4; no. 3; p. ENEURO.0114-17.2017
• Main Authors: Li, Ping, Stewart, Richard, Butler, Alice, Gonzalez-Cota, Ana Laura, Harmon, Steve, Salkoff, Lawrence
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 01.05.2017
• Subjects: Animals; Cations, Monovalent - metabolism; Cells, Cultured; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neurons - drug effects; Neurons - metabolism; New Research; Olfactory Bulb - drug effects; Olfactory Bulb - metabolism; Oocytes; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels - metabolism; Rats, Sprague-Dawley; Receptors, GABA-B - metabolism; Sodium - metabolism; Xenopus laevis; olfactory bulb; GABA-B; Baclofen; potassium channel; SLO2; Slick; mitral cell; persistent sodium current
• ISSN: 2373-2822; 2373-2822
• DOI: 10.1523/ENEURO.0114-17.2017

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 (INa ) and the sodium-activated potassium current (IK ), which is coupled to it. We find that the primary effect of GABA-B activation is to inhibit INa , which has the secondary effect of inhibiting IK 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 INa /IK 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 IK 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 IK blocking effect, thus enhancing the effectiveness of synaptic potentials.