Diverse subtypes of voltage-gated sodium channels(VGSCs)have been found throughout tissues of the brain,muscles and the heart.Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch(BmK)act as sodium channel-specific modulators and have therefore been widely used to study VGSCs.α-type neurotoxins,named BmK I,BmKαIV and BmK abT,bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs.In contrast,β-type neurotoxins,named BmK AS,BmK AS-1,BmK IT and BmK IT2,occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels.Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs,however,indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simpleα-type and β-type neurotoxin distinction.Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region-and/or speciesspecific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs.In this review,we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3-or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.
脑胶质瘤是中枢神经系统中最常见的脑肿瘤,尽管治疗水平在不断提高,但其治疗效果仍不理想。Stat3作为信号转导和转录活化蛋白(signal transduction and activator of transcription,Stat)家族的一个成员,对细胞的生长,存活和分化起到重要的调控作用。本文综述了Stat3蛋白的活化途径以及Stat3对脑胶质瘤增殖、凋亡、血管生成、分化等影响的研究。这些研究提示了Stat3有望成为脑胶质瘤治疗的潜在靶分子。
