Abstract
Neurons within the periaqueductal gray (PAG) have been implicated in the central regulation of pain signals by affecting the descending inhibitory pathway. Here we report on the functional role of presynaptic kainate receptors within the PAG. Using a conventional whole-cell patch clamp technique, we recorded GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) from mechanically isolated rat PAG neurons in the presence of 300nM tetrodotoxin and 20μM dl-2-amino-5-phosphonovaleric acid under voltage-clamp conditions. Kainic acid at a 10μM concentration significantly increased the frequency of GABAergic mIPSCs without affecting their amplitude, suggesting that kainic acid acts presynaptically to enhance spontaneous GABA release. The kainic acid-induced increase in mIPSC frequency was completely blocked by CNQX, a selective AMPA/kainate receptor antagonist. While neither AMPA nor NMDA affected GABAergic mIPSC frequency, ATPA, a selective agonist of GluR5-containing kainate receptors, increased GABAergic mIPSC frequency in a concentration-dependent manner. The kainic acid-induced increase in mIPSC frequency was completely suppressed either in the presence of 100μM Cd2+, a general voltage-dependent Ca2+ channel (VDCC) blocker, or in the Na+-free external solution. These results suggest that presynaptic kainate receptors have a low permeability to Ca2+, and that their activation elicits a presynaptic depolarization large enough to activate presynaptic VDCCs. Presynaptic kainate receptors on GABAergic nerve terminals appear to modulate GABAergic transmission, and in doing so may play an important role in the regulation of PAG neuron excitability.
Original language | English |
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Pages (from-to) | 72-78 |
Number of pages | 7 |
Journal | European Journal of Pharmacology |
Volume | 635 |
Issue number | 1-3 |
DOIs | |
State | Published - Jun 2010 |
Keywords
- GABAergic mIPSCs
- Kainate receptors
- PAG neurons
- Patch clamp
- Presynaptic facilitation