GABA(B) receptor activation inhibits N- and P/Q-type calcium channels in cultured lamprey sensory neurons

In lamprey, sensory transmission from mechanosensory receptors (dorsal cell s) to central neurons is presynaptically inhibited by GABA(B) receptor acti vation. The mechanisms underlying this effect were investigated using isola ted dorsal cells, where voltage-dependent calcium currents were recorded in the whole-cell configuration. Activation of GABA(B) receptors by baclofen decreased the peak amplitude of high voltage-activated (HVA) calcium curren ts and slowed the activation phase. The role of G-proteins in mediating the effects of baclofen was examined. Intracellular dialysis of GTP gamma S oc cluded the effects of baclofen. Intracellular dialysis of GDP beta S and pr eincubation in pertussis toxin both attenuated the effect of baclofen. Spec ific calcium channel blockers were used to study the types of HVA calcium c hannels involved in the GABA(B)-mediated modulation. The baclofen-induced i nhibition was not affected by the L-type calcium channel antagonist nimodip ine, but was partially blocked by the N-type blocker omega-conotoxin GVIA, and completely occluded by omega-conotoxin MVIIC, a blocker of both N- and P/Q-type channels. The pharmacology of dorsal cell GABA(B) receptors was st udied using two agonists, baclofen and CGP 27492, and four antagonists, CGP 35348, CGP 55845, phaclofen and saclofen. The inhibition induced by either of the two agonists was blocked by CGP 55845, phaclofen and saclofen. The antagonist CGP 35348 completely blocked the inhibition of HVA calcium curre nt induced by the agonist CGP 27492, but had no effect on baclofen-induced GABA(B) receptor activation. This study thus demonstrates that GABA(B) rece ptor activation in lamprey mechanosensory neurons inhibits N- and P/Q-type calcium channels in a voltage- and G-protein-dependent manner. (C) 1999 Pub lished by Elsevier Science B.V. All rights reserved.