ADENOVIRUS-MEDIATED EXPRESSION OF A VOLTAGE-GATED POTASSIUM CHANNEL IN-VITRO (RAT CARDIAC MYOCYTES) AND IN-VIVO (RAT-LIVER)
ADENOVIRUS-MEDIATED EXPRESSION OF A VOLTAGE-GATED POTASSIUM CHANNEL IN-VITRO (RAT CARDIAC MYOCYTES) AND IN-VIVO (RAT-LIVER)
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DOI：
10.1172/jci118103
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发表时间：
1995-08-01
影响因子：
15.9
通讯作者：
LAWRENCE, JH
中科院分区：
文献类型：
--
作者：
JOHNS, DC;NUSS, HB;LAWRENCE, JH
兴奋性主要由细胞膜中的离子通道的补充来控制，所述离子通道形成动作电位的轮廓。为了通过基因转移来修改兴奋性，我们创建了被设计为过表达果蝇Shaker钾通道（AdShK）的重组腺病毒。在体外，感染AdShK的多种哺乳动物细胞类型均表现出外源性通道的稳健表达，原代培养的心肌细胞记录到的自发动作电位与未感染的心肌细胞相比缩短，新生大鼠血管内输注AdShK诱导Shaker钾通道mRNA表达在肝脏中，并且可以从外植肝细胞中记录到大的钾电流，因此，重组腺病毒技术已被用于体外和体内基因转移离子通道基因，该基因被设计为改变细胞动作电位。在适当的靶向下，这种策略可用于心律失常、癫痫发作和肌强直性肌肉疾病的基因治疗。
Excitability is governed primarily by the complement of ion channels in the cell membrane that shape the contour of the action potential, To modify excitability by gene transfer, we created a recombinant adenovirus designed to overexpress a Drosophila Shaker potassium channel (AdShK). In vitro, a variety of mammalian cell types infected with AdShK demonstrated robust expression of the exogenous channel, Spontaneous action potentials recorded from cardiac myocytes in primary culture were abbreviated compared with noninfected myocytes, Intravascular infusion of AdShK in neonatal rats induced Shaker potassium channel mRNA expression in the liver, and large potassium currents could be recorded from explanted hepatocytes, Thus, recombinant adenovirus technology has been used for in vitro and in vivo gene transfer of ion channel genes designed to modify cellular action potentials, With appropriate targeting, such a strategy may be useful in gene therapy of arrhythmias, seizure disorders, and myotonic muscle diseases.