Involvement of batrachotoxin binding sites in ginsenoside-mediated voltage-gated Na super(+) channel regulation

• Published in: Brain research Vol. 1203; pp. 61 - 67
• Main Authors: Lee, J H, Lee, B H, Choi, SH, Yoon, I S, Shin, T J, Pyo, M K, Lee, S M, Kim, H C, Nah, SY
• Format: Journal Article
• Language: English
• Published: 08.04.2008
• Subjects: Panax ginseng
• ISSN: 0006-8993
• DOI: 10.1016/j.brainres.2008.01.078

Recently, we showed that the 20(S)-ginsenoside Rg sub(3) (Rg sub(3)), an active ingredient of Panax ginseng, inhibits rat brain Na sub(V)1.2 channel peak currents (I sub(N) sub(a)). Batrachotoxin (BTX) is a steroidal alkaloid neurotoxin and activates Na sub(V) channels through interacting with transmembrane domain-I-segment 6 (IS6) of channels. Recent report shows that ginsenoside inhibits BTX binding in rat brain membrane fractions. However, it needs to be confirmed whether biochemical mechanism is relevant physiologically and which residues of the BTX binding sites are important for ginsenoside regulations. Here, we demonstrate that mutations of BTX binding sites such as N418K and L421K of rat brain Na sub(V)1.2 and L437K of mouse skeletal muscle Na sub(V)1.4 channel reduce or abolish Rg sub(3) inhibition of I sub(N) sub(a) and attenuate Rg sub(3)-mediated depolarizing shift of the activation voltage and use-dependent inhibition. These results indicate that BTX binding sites play an important role in modifying Rg sub(3)-mediated Na super(+) channel properties.