Inhibition of Na+-dependent GABA uptake in isolated frog sensory nerve cell bodies by extra- and intracellular Li+.

The effect of Li+ on the Na+-dependent gamma-aminobutyric acid (GABA) uptake was investigated by examining the effects of external and internal Li+ ([Li]o and [Li]i) on GABA-gated Cl- current (ICl) in the frog dorsal root ganglion cells using the suction pipette technique which allows the internal perfusion under voltage-clamp condition. The suppression of GABA responses in the presence of external Na+ ([Na]o) was larger at lower than at higher GABA concentration. Replacement of [Na]o with Li+ completely removed the Na+ suppression, and GABA dose-response curve in Li+ external solution agreed well with that in Na+-free (Tris+) external solution. Either increasing [Li]i) or internal Na+ ([Na]i) at a constant [Na]o equally reduced the Na+-dependent suppression of GABA-gated ICl. The results indicate that both the [Li]o and [Li]i remove in different manner the [Na]o-dependent suppression of GABA-induced ICl:i.e. the [Li]o acts as a blocker of Na+-GABA co-transport mechanism while the increase of [Li]i decreases the Na+ electrochemical potential gradient across the soma membrane as well as [Na]i does.