| Abstract No.: | A-D1138 |
| Country: | Canada |
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| Title: | DIFFERENTIAL GABAA RECEPTOR KINETICS IN GAD65+ EXPRESSING INTERNEURONS IN THE DORSAL HORN |
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| Authors/Affiliations: | 1 Charalampos Labrakakis*; 1 Yves De Koninck;
1 Centre de Reserche Universite Laval Robert-Giffard, Québec, QC, Canada
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| Content: | GABAergic interneurons in the dorsal horn of the spinal cord play a pivotal role in the processing and modulation of the nociceptive sensory information. GABAergic signaling is a major contributor in balancing excitability in the neuronal circuits of superficial dorsal horn. Indeed, increased excitability due to disruption of GABAergic signaling is known to be involved in hyperalgesia and neuropathic pain.
We studied the properties of the GABAA-receptor mediated transmission in different cell types in the dorsal horn. In particular the kinetics of synaptic GABAA currents. We used transgenic mice that express green fluorescent protein (GFP) under the control of the promoter of the neuronal GABA synthesizing enzyme GAD65 (Erdelyi et al., 2002). Whole cell voltage clamp reordings were performed on GFP positive (GFP+) and GFP negative (GFP-) neurons in parasagittal spinal cord slices. Monosynaptically evoked (eIPSCs) and miniature (mIPSCs) GABAergic synaptic currents were isolated pharmacologically with APV, CNQX and strychnine.
Evoked GABAA synaptic current decays were well fit by a sum of two exponentials: A fast component tau(fast)= 35 ± 3 ms and a slow component tau(slow) = 161± 21 ms in GFP- neurons and tau(fast)= 45 ± 4 ms and tau(slow) = 398 ± 39 ms in GFP+ neurons respectively. The difference in the slow decay component between GFP+ and GFP- was statistically significant (p<0.001). In contrast, glycine receptor-mediated synaptic currents had comparable kinetics between the two cell populations (tau= 12.1 ± 1.5 ms for GFP- and tau = 12.3 ± 2.1 ms for GFP+ neurons). Slow decaying synaptic GABAA responses were also observed in recordings of mIPSCs indicating that it reflects the kinetics of the postsynaptic receptors and not variations in cleft neurotransmitter concentrations or asynchronous release. This has also been confirmed with the use of the GABA uptake blocker SKF89976A. The alpha5 subunit specific inverse agonist, L655708 affected the eIPSC decay in both GFP+ and GFP- neurons, indicating the presence of the alpha5 subunits in the superficial dorsal horn.
Our results show differences in the kinetics of synaptic GABAergic currents between inhibitory interneurons and unidentified neurons (including excitatory interneurons) in the superficial dorsal horn. These differences are due to intrinsic properties of the GABAA receptors on the neurons and could be attributed to differential subunit composition.
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