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KMID : 0355220100350040283
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Journal of Korean Academy Oral Medicine
2010 Volume.35 No. 4 p.283 ~ p.292
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Non-GABAA Receptor-Mediated Actions of Bicuculline Methiodide (BMI) on The Substantia Gelatinosa Neurons of Trigeminal Subnucleus Caudalis in Mice
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Choi Soon-Jeong
Han Seong-Kyu
Lee Kyung-Eun
Seo Bong-Jik
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Abstract
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Bicuculline is one of the most commonly used type A gamma aminobutyric acid (GABAA) receptor antagonists in electrophysiological research. Because of its poor water solubility, bicuculline quaternary ammonium salts such as bicuculline methiodide (BMI) and bicuculline methbromide (BMB) are preferred. However, a number of studies have shown that BMI has non-GABAA receptor mediated effects.
The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is implicated in the processing of nociceptive signaling. However, little is known about non-GABAergic action of BMI on the SG neurons of Vc in mice. This study investigated whether BMI has a non-GABA receptor mediated activity on SG neurons of Vc in mice using a whole cell patch clamp technique. The majority of SG neurons tested were depolarized by application of BMI (20 μM) in condition of a high Cl? pipette solution (n=36/54, 66.7%). 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 (PIC), a GABAA and GABAC receptor antagonist, blocked the GABA-induced response. Furthermore, BMI-induced membrane depolarization persisted in the presence of PIC or an antagonist mixture consisting of tetrodotoxin (TTX, Na? channel blocker), AP-5 (NMDA receptor antagonist), CNQX (non-NMDA glutamate receptor antagonist), and strychnine (glycine receptor antagonist). In addition, BMI induced inward current in voltage clamp mode, however BMB (bicuculline methbromide) and BMC (bicuculline methchloride), another water-soluble derivative of bicuculline are induced outward currents on SG neurons of Vc in mice at dose dependent manner.
These data demonstrate that BMI has non-GABAA receptor mediated action and suggest that the non-GABAA receptor mediated action can be mediated by iodide. Further studies are needed to investigate the precise action mechanism underlying the BMI-induced non-GABAA receptor mediated action on the SG neurons of Vc in mice.
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KEYWORD
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Bicuculline, Substantia gelatinosa, Trigeminal subnucleus caudalis
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