The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Presynaptic Mechanism Underlying Regulation of Transmitter Release by G Protein Coupled Receptors

  • Takahashi, Tomoyuki (Department of Neurophysiology, University of Tokyo Graduate School of Medicine) ;
  • Kajikawa, Yoshinao (Department of Neurophysiology, University of Tokyo Graduate School of Medicine) ;
  • Kimura, Masahiro (Department of Neurophysiology, University of Tokyo Graduate School of Medicine) ;
  • Saitoh, Naoto (Department of Neurophysiology, University of Tokyo Graduate School of Medicine) ;
  • Tsujimoto, Tetsuhiro (Department of Neurophysiology, University of Tokyo Graduate School of Medicine)
  • Published : 2004.04.21
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Abstract

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 $GABA_B$ receptors, group III metabotropic glutamate receptors (mGluRs), adenosine $A_1$ receptors, or adrenaline ${\alpha}2$ receptors, attenuate evoked transmitter release via inhibiting voltage-activated $Ca^{2+}$ currents without affecting voltage-activated $K^+$ currents or inwardly rectifying $K^+$ currents. Furthermore, inhibition of voltage-activated $Ca^{2+}$ currents fully explains the magnitude of GPCR-mediated presynaptic inhibition, indicating no essential involvement of exocytotic mechanisms in the downstream of $Ca^{2+}$ 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 $Ca^{2+}$ currents $(Ip_{Ca})$, suggesting that $G{\beta}{\gamma}$ mediates 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.

Keywords

References

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