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KMID : 0848120080330040217
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International Journal of Oral Biology
2008 Volume.33 No. 4 p.217 ~ p.221
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Bicuculline Methiodide (BMI) Induces Membrane Depolarization of The Trigeminal Subnucleus Caudalis Substantia Gelatinosa Neuron in Mice Via Non-GABAA Receptor-Mediated Action
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Yin Hua
Park Soo-Joung
Suh Bong-Jik
Park Seon-Ah
Han Seong-Kyu
Choi Soon-Jeong
Bhattarai Janardhan P.
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Abstract
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Bicuculline is one of the most commonly used GABAA receptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternary ammonium salts such as bicuculline methiodide (BMI) and bicuculline methbromide are preferred. However, a number of studies have shown that BMI has non-GABAA receptormediated
effects. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is implicated in the processing of nociceptive signaling. In this study, we investigated whether BMI has non-GABA receptormediated activity in Vc SG neurons using a whole cell patch clamp technique. SG neurons were depolarized by application of BMI (20 μM) using a high Cl - pipette solution. GABA (30-100 μM) also induced membrane depolarization of SG neuron. Although BMI is known to be a GABAA receptor antagonist, GABA-induced membrane depolarization was enhanced by co-application with BMI. However, free base bicuculline (fBIC) and picrotoxin (PTX), a GABAA and GABAC receptor antagonist, blocked the GABAinduced response. Furthermore, BMI-induced membrane depolarization persisted in the presence of PTX or an
antagonist cocktail consisting of tetrodotoxin (Na+ channel blocker), AP-5 (NMDA receptor antagonist), CNQX (non-
NMDA receptor antagonist), and strychnine (glycine receptor antagonist). Thus BMI induces membrane depolarization by directly acting on postsynaptic Vc SG neurons in a manner which is independent of GABAA receptors. These results suggest that other unknown mechanisms may be involved in BMI-induced membrane depolarization.
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KEYWORD
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Bicuculline methiodide, substantia gelatinosa neuron, trigeminal subnucleus caudalis, whole cell recording
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