International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Bicuculline Methiodide (BMI) Induces Membrane Depolarization of The Trigeminal Subnucleus Caudalis Substantia Gelatinosa Neuron in Mice Via Non-$GABA_A$ Receptor-Mediated Action

  • Yin, Hua (Department of Oral Physiology, Chonbuk National University) ;
  • Park, Seon-Ah (Department of Oral Physiology, Chonbuk National University) ;
  • Choi, Soon-Jeong (Department of Oral Medicine, School of Dentistry & Institute of Oral Bioscience, Chonbuk National University) ;
  • Bhattarai, Janardhan P. (Department of Oral Physiology, Chonbuk National University) ;
  • Park, Soo-Joung (Department of Oral Physiology, Chonbuk National University) ;
  • Suh, Bong-Jik (Department of Oral Medicine, School of Dentistry & Institute of Oral Bioscience, Chonbuk National University) ;
  • Han, Seong-Kyu (Department of Oral Physiology, Chonbuk National University)
  • Published : 2008.12.31
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Abstract

Bicuculline is one of the most commonly used $GABA_A$ 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-$GABA_A$ receptor-mediated 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 receptor-mediated activity in Vc SG neurons using a whole cell patch clamp technique. SG neurons were depolarized by application of BMI ($20{\mu}M$) using a high $Cl^-$ pipette solution. GABA ($30-100{\mu}M$) also induced membrane depolarization of SG neuron. Although BMI is known to be a $GABA_A$ receptor antagonist, GABA-induced membrane depolarization was enhanced by co-application with BMI. However, free base bicuculline (fBIC) and picrotoxin (PTX), a $GABA_A$ and $GABA_C$ receptor antagonist, blocked the GABA-induced 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 $GABA_A$ receptors. These results suggest that other unknown mechanisms may be involved in BMI-induced membrane depolarization.

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References

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