Metabotropic GABA receptors facilitate L-type and inhibit N-type calcium channels in single salamander retinal neurons

1. Whole-cell voltage clamp experiments were performed on isolated spiking retinal neurons from the salamander retina. Calcium channel currents were s tudied using barium as the charge carrier while potassium and sodium curren ts were suppressed with TEA and TTX, respectively. 2. Baclofen, a metabotropic GABA receptor agonist, both enhanced and suppre ssed high-voltage-activated calcium channel current. Baclofen facilitated a n L-type channel current, and this effect was not voltage dependent. As rep orted previously, baclofen inhibited an N-type channel current and this act ion was voltage dependent. 3. While the suppressive effect was mediated by a fast-acting, direct G-pro tein action, the facilitatory effect was slower and was blocked by inhibito rs of protein kinase C (PKC), either GF-109203x or the PKC(19-36) sequence fragment. 4. The pharmacology of the inhibitory and facilitatory responses differed. Commonly used antagonists of metabotropic GABA receptors, CGP35348 and CGP5 5845, were more potent antagonists of the inhibitory response. Similarly, a selective agonist at the metabotropic GABA receptor, APMPA, was also more effective in eliciting the inhibitory response. 5. These observations indicate that there may be two baclofen-sensitive met abotropic GABA receptors with opposing effects on calcium channel current. This is the first description of a facilitatory action of GABA(B) receptors and indicates that GABA may not function exclusively as an inhibitory tran smitter.