Partial compensation for N-type Ca(2+) channel loss by P/Q-type Ca(2+) channels underlines the differential release properties supported by these channels at cerebrocortical nerve terminals.

N-type and P/Q-type Ca(2+) channels support glutamate release at central synapses. To determine whether the glutamate release mediated by these channels exhibits distinct properties, we have isolated each release component in cerebrocortical nerve terminals from wild-type mice by specifically blocking N-type Ca(2+) channels with omega-conotoxin-GVIA and P/Q-type Ca(2+) channels with omega-agatoxin-IVA. In addition, we have determined the release properties at terminals from mice lacking the alpha(1B) subunit of N-type channels (Ca(v) 2.

Pre-synaptic GABA receptors inhibit glutamate release through GIRK channels in rat cerebral cortex.

Neuronal G protein-gated inwardly rectifying potassium (GIRK) channels mediate the slow inhibitory effects of many neurotransmitters post-synaptically. However, no evidence exists that supports that GIRK channels play any role in the inhibition of glutamate release by GABA(B) receptors. In this study, we show for the first time that GABA(B) receptors operate through two mechanisms in nerve terminals from the cerebral cortex.

The inhibition of release by mGlu7 receptors is independent of the Ca2+ channel type but associated to GABAB and adenosine A1 receptors.

Neurotransmitter release is inhibited by G-protein coupled receptors (GPCRs) through signalling pathways that are negatively coupled to Ca2+ channels and adenylyl cyclase. Through Ca2+ imaging and immunocytochemistry, we have recently shown that adenosine A1, GABAB and the metabotropic glutamate type 7 receptors coexist in a subset of cerebrocortical nerve terminals. As these receptors inhibit glutamate release through common intracellular signalling pathways, their co-activation occluded each other responses.

The coexistence of multiple receptors in a single nerve terminal provides evidence for pre-synaptic integration.

Excitatory synaptic transmission is inhibited by G protein coupled receptors, including the adenosine A(1), GABA(B), and metabotropic glutamate receptor 7. These receptors are present in nerve terminals where they reduce the release of glutamate through activating signaling pathways negatively coupled to Ca(2+) channels and adenylyl cyclase. However, it is not clear whether these receptors operate in distinct subpopulations of nerve terminals or if they are co-expressed in the same nerve terminals, despite the functional consequences that such distributions may have on synaptic transmission.