Voltage-gated sodium channels (VGSCs) are pivatol transmembrane proteins responsible for initiating and conducting action potentials in excitable cells.Diverse subtypes of VGSCs are found throughout the tissues like brain, muscle and heart.Neurotoxins (60-76 amino acid residues) purified from the venom of Asian scorpion Buthus martensi Karsch (BmK) have been investigated to be sodium channel-specific modulators.The α neurotoxins named as BmK I ,BmK αⅣ and BmK abT binding to receptor site 3 of sodium channels, could strongly prolong the inactivation phase of sodium channels.On the contrary, the β neurotoxins named as BmK AS, BmK AS-1 ,BmK IT and BmK IT2 occupying receptor site 4 of sodium channels, could suppress the peak currents and hyperpolarize the activation kinetics of sodium channels.However, undertaken binding assays uncoverer the bilateral relationship between toxins and VGSCs may exhibit more complexed diversity in that pharmacological sensitivity of VGSC subtypes to different modulators and structural versatility of VGSC subtypes could also stand to be essential elements.Thus, it would be significant to explore the possible dynamic interaction mechanisms of either site 3-or site 4-specific modulators and region-and/or species-specific of sodium channel subtypes for better understanding the physiological and pharmacological roles of diverse VGSCs subtypes.This review will cover the pharmacological and structural diversity of VGSCs through elucidating the binding features of site 3-or site 4-specific modulators on VGSC subtype-distinct synaptosomes.