A variety of G protein coupled receptors (GPCRs) are expressed in the presynaptic terminals of central and peripheral synapses and play regulatory roles in transmitter release. The patch-clamp whole-cell recording technique, applied to the calyx of Held presynaptic terminal in brainstem slices of rodents, has made it possible to directly examine intracellular mechanisms underlying the GPCR-mediated presynaptic inhibition. At the calyx of Held, bath-application of agonists for GPCRs such as GABAB receptors, group III metabotropic glutamate receptors (mGluRs), adenosine A1 receptors, or adrenaline alpha2 receptors, attenuate evoked transmitter release via inhibiting voltage-activated Ca2+ currents without affecting voltage-activated K+ currents or inwardly rectifying K+ currents. Furthermore, inhibition of voltage-activated Ca2+ currents fully explains the magnitude of GPCR-mediated presynaptic inhibition, indicating no essential involvement of exocytotic mechanisms in the downstream of Ca2+ influx. Direct loadings of G protein beta gamma subunit (G beta gamma) into the calyceal terminal mimic and occlude the inhibitory effect of a GPCR agonist on presynaptic Ca2+ currents (IpCa), suggesting that G beta gammamediates presynaptic inhibition by GPCRs. Among presynaptic GPCRs glutamate and adenosine autoreceptors play regulatory roles in transmitter release during early postnatal period when the release probability (p) is high, but these functions are lost concomitantly with a decrease in p during postnatal development.
Adenosine ; Autoreceptors ; Brain Stem ; Epinephrine ; Glutamic Acid ; GTP-Binding Proteins* ; Patch-Clamp Techniques ; Presynaptic Terminals ; Receptor, Adenosine A1 ; Receptors, G-Protein-Coupled* ; Receptors, Metabotropic Glutamate ; Rodentia ; Synapses