Gabapentin may inhibit synaptic transmission in the mouse spinal cord dorsal horn through a preferential block of P/Q-type Ca2+ channels
| Autor: | Hanns Ulrich Zeilhofer, Seifollah Ahmadi, Katharina Bayer |
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| Přispěvatelé: | University of Zurich, Zeilhofer, Hanns Ulrich |
| Rok vydání: | 2004 |
| Předmět: |
Male
Cyclohexanecarboxylic Acids 2804 Cellular and Molecular Neuroscience 10050 Institute of Pharmacology and Toxicology 610 Medicine & health Pharmacology GABAB receptor Neurotransmission Acetates Inhibitory postsynaptic potential Synaptic Transmission gamma-Aminobutyric acid Cellular and Molecular Neuroscience Mice Calcium Channels N-Type Spinal Cord Dorsal Horn medicine Animals Amines gamma-Aminobutyric Acid Mice Inbred BALB C Dose-Response Relationship Drug Chemistry GABAA receptor Glutamate receptor Neural Inhibition Posterior Horn Cells 3004 Pharmacology nervous system Spinal Cord Excitatory postsynaptic potential 570 Life sciences biology Female Gabapentin medicine.drug |
| DOI: | 10.5167/uzh-4713 |
| Popis: | Gabapentin is a lipophilic analog of gamma-amino butyric acid (GABA) with therapeutic activity against certain forms of epilepsy and neuropathic pain. Despite its structural similarity to GABA, it does not bind GABAA or GABAB receptors and the mechanism, especially of its analgesic action, has remained elusive. Here, we have studied its effects on synaptic transmission mediated by the major spinal fast excitatory and inhibitory neurotransmitters, L-glutamate and glycine, in the superficial layers of the spinal cord dorsal horn, a CNS area, which is critically involved in nociception. Gabapentin reversibly reduced evoked excitatory postsynaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA-EPSCs) and inhibitory postsynaptic currents mediated by glycine (gly-IPSCs). Inhibition of AMPA-EPSCs and gly-IPSCs occurred with similar potencies (approximately 10-50 nM) and by about the same degree (approximately 40% at 1 microM). Gabapentin did not affect membrane currents elicited by exogenously applied glutamate or glycine arguing against a postsynaptic site of action. Selective blockade of N-type Ca2+ channels with omega-conotoxin GVIA dramatically increased and blockade of P/Q-type channels with omega-agatoxin IVA strongly attenuated inhibition of evoked synaptic transmission by gabapentin. These results show that gabapentin affects both excitatory and inhibitory spinal neurotransmission via a presynaptic mechanism which preferentially involves P/Q-type Ca2+ channels. |
| Databáze: | OpenAIRE |
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