Reduction of hERG potassium currents by hyperosmolar solutions
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- 作者：Fumie Yabuuchi ; Rolf Beckmann ; Erich Wettwer ; Christa Hegele-Hartung ; Jü ; rgen F. Heubach
- 关键词：Patch-clamp technique ; Human ether-a-go-go related gene ; hERG ; CHO cells ; d-mannitol ; Hyperosmolar solution
- 刊名：European Journal of Pharmacology
- 出版年：2007
- 出版时间：2 July 2007
- 年：2007
- 卷：566
- 期：1-3
- 页码：222-225
- 全文大小：279 K
文摘
We investigated the effects of hyperosmolar solutions on human ether-a-go-go related gene (hERG) potassium currents in chinese hamster ovary (CHO) cells. The addition of d-mannitol to the external solution caused cell shrinkage and reduced current amplitude. The effects were at least partially reversible. Exposure to 108 mM mannitol decreased current amplitude by 57 ± 13 % . Major effects on current–voltage relations were not observed. Exposure to 308 mM mannitol reduced the current by 89 ± 5 % , i.e. comparable to the block induced by 1 μM of the selective hERG channel blocker E-4031. We conclude that the investigation of hyperosmolar drug formulations requires control solutions of comparable osmolarity to separate specific drug effects from non-specific effects of hyperosmolarity.