GTP-binding protein beta gamma subunits mediate presynaptic calcium current inhibition by GABA(B) 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 gamma-aminobutyric acid type B receptors (GABA(B) receptors) or metabotropic glutamate receptors inhibits presynaptic P/Q-type Ca(2+) 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 beta gamma subunits (G beta gamma) directly into the calyceal nerve terminal through whole-cell patch pipettes. G beta gamma slowed the activation of presynaptic Ca(2+) currents (I(pCa)) and attenuated its amplitude in a manner similar to the externally applied baclofen, a GABA(B) receptor agonist. The effects of both G beta gamma and baclofen were relieved after strong depolarization of the nerve terminal. In addition, G beta gamma partially occluded the inhibitory effect of baclofen on I(pCa). In contrast, guanosine 5'-O-(3-thiotriphosphate)-bound G(o)alpha loaded into the calyx had no effect. Immunocytochemical examination revealed that the subtype of G proteins G(o), but not the G(i), 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 G(o) beta gamma subunits with presynaptic Ca(2+) channels.
Kajikawa
Y
Y
Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033, Japan.
Saitoh
N
N
Takahashi
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D004594:Electrophysiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D015220:Calcium Channels; D018079:Receptors, GABA; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium