G-protein-coupled GABAB receptors inhibit Ca2+ channels and modulate transmitter release in descending turtle spinal cord terminal synapsing motoneurons
✍ Scribed by Alberto Castro; Justo Aguilar; David Elias; Ricardo Felix; Rodolfo Delgado-Lezama
- Book ID
- 102111969
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 423 KB
- Volume
- 503
- Category
- Article
- ISSN
- 0021-9967
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✦ Synopsis
Abstract
Presynaptic γ‐aminobutyric acid type B receptors (GABA~B~Rs) regulate transmitter release at many central synapses by inhibiting Ca^2+^ channels. However, the mechanisms by which GABA~B~Rs modulate neurotransmission at descending terminals synapsing on motoneurons in the spinal cord remain unexplored. To address this issue, we characterized the effects of baclofen, an agonist of GABA~B~Rs, on the monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in motoneurons by stimulation of the dorsolateral funiculus (DLF) terminals in a slice preparation from the turtle spinal cord. We found that baclofen depressed neurotransmission in a dose‐dependent manner (IC~50~ of ∼2 μM). The membrane time constant of the motoneurons did not change, whereas the amplitude ratio of the evoked EPSPs in response to a paired pulse was altered in the presence of the drug, suggesting a presynaptic mechanism. Likewise, the use of N‐ and P/Q‐type Ca^2+^ channel antagonists (ω‐conotoxin GVIA and ω‐agatoxin IVA, respectively) also depressed EPSPs significantly. Therefore, these channels are likely involved in the Ca^2+^ influx that triggers transmitter release from DLF terminals. To determine whether the N and P/Q channels were regulated by GABA~B~R activation, we analyzed the action of the toxins in the presence of baclofen. Interestingly, baclofen occluded ω‐conotoxin GVIA action by ∼50% without affecting ω‐agatoxin IVA inhibition, indicating that the N‐type channels are the target of GABA~B~Rs. Lastly, the mechanism underlying this effect was further assessed by inhibiting G‐proteins with N‐ethylmaleimide (NEM). Our data show that EPSP depression caused by baclofen was prevented by NEM, suggesting that GABA~B~Rs inhibit N‐type channels via G‐protein activation. J. Comp. Neurol. 503:642–654, 2007. © 2007 Wiley‐Liss, Inc.