Bicuculline Methiodide (BMI) Induces Membrane Depolarization of The Trigeminal Subnucleus Caudalis Substantia Gelatinosa Neuron in Mice Via Non-GABAA Receptor-Mediated Action
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Bicuculline is one of the most commonly used GABAAreceptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternaryammonium salts such as bicuculline methiodide (BMI) andbicuculline methbromide are preferred. However, a numberof studies have shown that BMI has non-GABAA receptormediatedeffects. The substantia gelatinosa (SG) of thetrigeminal subnucleus caudalis (Vc) is implicated in theprocessing of nociceptive signaling. In this study, weinvestigated whether BMI has non-GABA receptormediatedactivity in Vc SG neurons using a whole cell patchclamp technique. SG neurons were depolarized byapplication of BMI (20 μM) using a high Cl-pipette solution. GABA (30-100 μM) also induced membrane depolarizationof SG neuron. Although BMI is known to be a GABAAreceptor antagonist, GABA-induced membrane depolarizationwas enhanced by co-application with BMI. However,free base bicuculline (fBIC) and picrotoxin (PTX), a GABAAand GABAC receptor antagonist, blocked the GABAinducedresponse. Furthermore, BMI-induced membranedepolarization persisted in the presence of PTX or anantagonist cocktail consisting of tetrodotoxin (Na+ channelblocker), AP-5 (NMDA receptor antagonist), CNQX (non-NMDA receptor antagonist), and strychnine (glycinereceptor antagonist). Thus BMI induces membranedepolarization by directly acting on postsynaptic Vc SGneurons in a manner which is independent of GABAAreceptors. These results suggest that other unknownmechanisms may be involved in BMI-induced membranedepolarization.
Abstract
Bicuculline is one of the most commonly used GABAAreceptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternaryammonium salts such as bicuculline methiodide (BMI) andbicuculline methbromide are preferred. However, a numberof studies have shown that BMI has non-GABAA receptormediatedeffects. The substantia gelatinosa (SG) of thetrigeminal subnucleus caudalis (Vc) is implicated in theprocessing of nociceptive signaling. In this study, weinvestigated whether BMI has non-GABA receptormediatedactivity in Vc SG neurons using a whole cell patchclamp technique. SG neurons were depolarized byapplication of BMI (20 μM) using a high Cl-pipette solution. GABA (30-100 μM) also induced membrane depolarizationof SG neuron. Although BMI is known to be a GABAAreceptor antagonist, GABA-induced membrane depolarizationwas enhanced by co-application with BMI. However,free base bicuculline (fBIC) and picrotoxin (PTX), a GABAAand GABAC receptor antagonist, blocked the GABAinducedresponse. Furthermore, BMI-induced membranedepolarization persisted in the presence of PTX or anantagonist cocktail consisting of tetrodotoxin (Na+ channelblocker), AP-5 (NMDA receptor antagonist), CNQX (non-NMDA receptor antagonist), and strychnine (glycinereceptor antagonist). Thus BMI induces membranedepolarization by directly acting on postsynaptic Vc SGneurons in a manner which is independent of GABAAreceptors. These results suggest that other unknownmechanisms may be involved in BMI-induced membranedepolarization.
참고문헌 (21)
- Bormann J, "The 'ABC' of GABA receptors", TRENDS IN PHARMACOLOGICAL SCIENCES, 21, pp.16~19 (2000)
- Bracci E, "Spontaneous rhythmic bursts induced by pharmacological block of inhibition in lumbar motoneurons of the neonatal rat spinal cord", JOURNAL OF NEUROPHYSIOLOGY, 75, pp.640~647 (1996)
- Cazalets JR, "GABAergic inactivation of the central pattern generators for locomotion in isolated neonatal rat spinal cord", Journal of Physiology, 474, pp.173~181 (1994)
- Cowley KC, "Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord", Journal of Neurophysiology, 74, pp.1109~1117 (1995)
- Curtis DR, "GABA, bicuculline and central inhibition", Nature, 226, pp.1222~1224 (1970)
- Debarbieux F, "Effect of bicuculline on thalamic activity: a direct blockade of IAHP in reticularis neurons", Journal of Neurophysiology, 79, pp.2911~2918 (1998)
- Feigenspan A, "Pharmacology of GABA receptor Cl- channels in rat retinal bipolar cells", Nature, 361, pp.159~262 (1993)
- Han SK, "Norepinephrine suppresses gonadotropinreleasing hormone neuron excitability in the adult mouse", Endocrinology, 149, pp.1129~1135 (2008)
- Han SK, "Noradrenaline inhibits substantia gelatinosa neurons in mice trigeminal subnucleus caudalis via alpha(2) and beta adrenoceptors", Neuroscience Letters, 411, pp.92~97 (2007)
- Heyer EJ, "Bicuculline: A convulsant with synaptic and nonsynaptic actions", Neurology, 31, pp.1381~1390 (1981)
- Johnson SW, "Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+currents", Neuroscience Letters, 231, pp.13~16 (1997)
- Johnston GA, "GABAc receptors: relatively simple transmittergated ion channels?", TRENDS IN PHARMACOLOGICAL SCIENCES, 17, pp.319~323 (1996)
- Jovanovic K, "Effects of inhibitory neurotransmitters on the mudpuppy (Necturus maculatus) locomotor pattern in vitro", Experimental Brain Research, 129, pp.172~184 (1999)
- Olsen RW, "Studies on the neuropharmacological activity of bicuculline and related compounds", Brain Research, 102, pp.283~299 (1976)
- Park JS, "Bicucullineresistant, Cl-dependent GABA response in the rat spinal dorsal horn", NEUROSCIENCE RESEARCH, 33, pp.261~268 (1999)
- Qian H, "Novel GABA responses from roddriven retinal horizontal cells", Nature, 361, pp.162~164 (1993)
- Sessle, B.J, "Mechanisms of trigeminal and occipital pain", Pain Reviews, 3, pp.91~116 (1996)
- Seutin V, "Recent advances in the pharmacology of quaternary salts of bicuculline", TRENDS IN PHARMACOLOGICAL SCIENCES, 20, pp.268~270
- Seutin V, "Evidence for a non-GABAergic action of quaternary salts of bicuculline on dopaminergic neurones", Neuropharmacology, 36, pp.1653~1657 (1997)
- Shi WX, "GABA synapses formed in vitro by local axon collaterals of nucleus accumbens neurons", Journal of Neuroscience, 14, pp.4548~4560 (1994)
- Zhang ZW, "Bicuculline blocks nicotinic acetylcholine response in isolated intermediate lobe cells of the pig", British Journal of Pharmacology, 102, pp.19~22 (1991)