Reduction of hERG potassium currents by hyperosmolar solutions.
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 microM 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.
Yabuuchi
Fumie
F
Safety Pharmacology, Bayer Schering Pharma AG, Berlin, Germany. fumie.yabuuchi@bayerhealthcare.com
Beckmann
Rolf
R
Wettwer
Erich
E
Hegele-Hartung
Christa
C
Heubach
Jürgen F
JF
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D006801:Humans; D008353:Mannitol / Q000737:chemistry / Q000494:pharmacology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D012996:Solutions
D051638:Ether-A-Go-Go Potassium Channels; D012996:Solutions; D008353:Mannitol