Co-expression of Metabotropic Glutamate Receptor 7 and N-type Ca2+ Channels in Single Cerebrocortical Nerve Terminals of Adult Rats

Abstract

The modulation of calcium channels by metabotropic glutamate receptors (mGluRs) is a key event in the finetuning of neurotransmitter release. Here we report that, in cerebrocortical nerve terminals of adult rats, the inhibition of glutamate release is mediated by mGluR7. In this preparation, the major component of glutamate release is supported by P/Q-type Ca 2؉ channels (72.7%). However, mGluR7 selectively reduced the release component that is associated with N-type Ca 2؉ channels (29.9%). Inhibition of P/Q channels by mGluR7 is not masked by the higher efficiency of these channels in driving glutamate release when compared with N-type channels. Thus, activation of mGluR7 failed to reduce the release associated with P/Q channels when the extracellular calcium concentration, ([Ca 2؉ ] o ), was reduced from 1.3 to 0.5 mM. Through Ca 2؉ imaging, we show that Ca 2؉ channels are distributed in a heterogeneous manner in individual nerve terminals. Indeed, in this preparation, nerve terminals were observed that contain N-type (31.1%; conotoxin GVIA-sensitive) or P/Qtype (64.3%; agatoxin IVA-sensitive) channels or that were insensitive to these two toxins (4.6%). Interestingly, the great majority of the responses to L-AP4 (95.4%) were observed in nerve terminals containing Ntype channels. This specific co-localization of mGluR7 and N-type Ca 2؉ -channels could explain the failure of the receptor to inhibit the P/Q channel-associated release component and also reveal the existence of specific targeting mechanisms to localize the two proteins in the same nerve terminal subset.

Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells

“…Thus, it seems that human chromaffin cells show a nonuniform distribution of N-and P/Q-type channels. These findings are in line with observations in neuron cultures, in which relative proportions of N-and P/Q-type channels have been reported to vary at different synapses [38][39][40][41][42][43][44][45][46][47]. Neuromodulators can differentially affect specific Ca 2+ channel subtypes [48][49][50][51].…”

Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca2+ signalling in hippocampal neurons

“…We used hippocampal neurons in culture, which are formed by approximately 80% of glutamatergic neurons (pyramidal cells) vs. 20% of GABAergic neurons (interneurons and granular cells); similar rates has been described in cortex primary culture (Millán et al, 2003). As shown in Fig.…”

In Vitro Pharmacological Characterization of Novel Isoxazolopyridone Derivatives as Allosteric Metabotropic Glutamate Receptor 7 Antagonists

“…MMPIP and MDIP might have different affinities for two confirmations of mGluR7 coupling to G␣ 15 and G i/o . It may therefore be worth evaluating the activities of isoxazolopyridone derivatives toward other functional responses (Saugstad et al, 1996, Perroy et al, 2000Millá n et al, 2002Millá n et al, , 2003 to further understand their signal pathway-dependent activities.…”