Abstract
Reduction of transmitter release by activation of presynaptic G protein-coupled receptors (GPCRs) is a major mechanism in the presynaptic inhibition. In many neuronal structures, GPCR agonists, such as adenosine, exert a presynaptic inhibitory effect through inhibiting N-type voltage-dependent calcium channels (VDCCs). To understand how the functional coupling between G proteins and VDCCs is regulated, we analyzed the effect of adenosine on the synaptic transmission from the primary afferents to the second-order neurons in the nucleus tractus solitarii in the slices from the mice lacking α1B subunit of N-type VDCCs (CaV2.2−/−). Both in the wild type and CaV2.2−/− mice, adenosine decreased the amplitude of evoked EPSC with similar magnitude and time course. This effect was mimicked by CPA, blocked by DPCPX and accompanied by an increase in the paired-pulse ratio, indicating an involvement of presynaptic A1 receptors. Whereas ω-conotoxin GVIA occluded the inhibitory effect of adenosine in the wild type mice, adenosine significantly reduced EPSC amplitude even in the presence of ω-conotoxin GVIA, ω-agatoxin IVA and NiCl2 in CaV2.2−/−. These results imply an unidentified mechanism enabling the lack of the G protein target at the presynaptic terminal to lead to a compensatory replacement of another target so that the function of GPCR in regulating transmitter release could be conserved. [Jpn J Physiol 55 Suppl:S155 (2005)]
