Avanzini Giuliano, Franceschetti Silvana
Istituto Nazionale Neurologico C Besta, Milan, Italy.
Lancet Neurol. 2003 Jan;2(1):33-42. doi: 10.1016/s1474-4422(03)00265-5.
The ionic currents that underlie the mechanisms of epileptogenesis have been systematically characterised in different experimental preparations. The recent elucidation of the molecular structures of most membrane channels and receptors has enabled structure-function analyses in both physiological and pathophysiological conditions. The neurophysiological and biomolecular features of epileptogenic mechanisms that putatively account for human epilepsies are summarised in this review. Particular emphasis is given to epilepsies that are associated with genetically determined alterations of ligand-gated and voltage-gated ion channels. Changes in ionic currents that flow through sodium, potassium, and calcium channels can lead to different types of epilepsies. Inherited or acquired changes that alter the function of receptors for acetylcholine, glutamate, and gamma-aminobutryic acid are also involved. better understanding of the role of these epileptogenic mechanisms will promote new advances in the development of selective and targeted antiepileptic drugs.
在不同的实验准备中，已经系统地对构成癫痫发生机制基础的离子电流进行了表征。最近大多数膜通道和受体分子结构的阐明，使得在生理和病理生理条件下都能进行结构-功能分析。本综述总结了可能导致人类癫痫的癫痫发生机制的神经生理和生物分子特征。特别强调了与配体门控和电压门控离子通道的基因决定改变相关的癫痫。流经钠、钾和钙通道的离子电流变化可导致不同类型的癫痫。改变乙酰胆碱、谷氨酸和γ-氨基丁酸受体功能的遗传或后天变化也有涉及。更好地理解这些癫痫发生机制的作用将促进选择性和靶向抗癫痫药物开发的新进展。
