GTP-binding protein bg subunits mediate presynaptic calcium current inhibition by GABAB receptor

A variety of GTP-binding protein (G protein)-coupled receptors are expressed at the nerve terminals of central synapses and play modulatory roles in transmitter release. At the calyx of Held, a rat auditory brainstem synapse, activation of presynaptic g-aminobutyric acid type B receptors (GABAB receptors) or metabotropic glutamate receptors inhibits presynaptic PyQ-type Ca21 channel currents via activation of G proteins, thereby attenuating transmitter release. To identify the heterotrimeric G protein subunits involved in this presynaptic inhibition, we loaded G protein bg subunits (Gbg) directly into the calyceal nerve terminal through whole-cell patch pipettes. Gbg slowed the activation of presynaptic Ca21 currents (IpCa) and attenuated its amplitude in a manner similar to the externally applied baclofen, a GABAB receptor agonist. The effects of both Gbg and baclofen were relieved after strong depolarization of the nerve terminal. In addition, Gbg partially occluded the inhibitory effect of baclofen on IpCa. In contrast, guanosine 5*-O-(3-thiotriphosphate)-bound Goa loaded into the calyx had no effect. Immunocytochemical examination revealed that the subtype of G proteins Go, but not the Gi, subtype, is expressed in the calyceal nerve terminal. These results suggest that presynaptic inhibition mediated by G protein-coupled receptors occurs primarily by means of the direct interaction of Go bg subunits with presynaptic Ca21 channels.