Johns D C, Marx R, Mains R E, O'Rourke B, Marbán E
Section of Molecular and Cellular Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurosci. 1999 Mar 1;19(5):1691-7. doi: 10.1523/JNEUROSCI.19-05-01691.1999.
Graded, reversible suppression of neuronal excitability represents a logical goal of therapy for epilepsy and intractable pain. To achieve such suppression, we have developed the means to transfer "electrical silencing" genes into neurons with sensitive control of transgene expression. An ecdysone-inducible promoter drives the expression of inwardly rectifying potassium channels in polycistronic adenoviral vectors. Infection of superior cervical ganglion neurons did not affect normal electrical activity but suppressed excitability after the induction of gene expression. These experiments demonstrate the feasibility of controlled ion channel expression after somatic gene transfer into neurons and serve as the prototype for a novel generalizable approach to modulate excitability.
对神经元兴奋性进行分级、可逆性抑制是癫痫和顽固性疼痛治疗的合理目标。为实现这种抑制，我们已开发出将“电沉默”基因导入神经元并对转基因表达进行灵敏控制的方法。蜕皮激素诱导型启动子驱动多顺反子腺病毒载体中内向整流钾通道的表达。颈上神经节神经元感染后，正常电活动未受影响，但基因表达诱导后兴奋性受到抑制。这些实验证明了将体细胞基因转移到神经元后可控离子通道表达的可行性，并为调节兴奋性的一种新型通用方法提供了原型。
