[3H]dofetilide binding in SHSY5Y and HEK293 cells expressing a HERG-like K+ channel?

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Finlayson K, Pennington AJ, Kelly JS

[3H]dofetilide binding in SHSY5Y and HEK293 cells expressing a HERG-like K+ channel?

Eur J Pharmacol. 2001 Feb 2;412(3):203-12.

PubMed ID

11166283 [ View in PubMed

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Abstract

The pharmacological characteristics of [3H]dofetilide binding in SHSY5Y, HEK293 and CHO-K1 cells were examined, and in parallel whole cell recordings used to characterise HERG-like K+ currents. Dofetilide affinity was similar in the human cell lines, SHSY5Y (Kd=99.6 nM) and HEK293 (Kd=102.9 nM), but 10 times lower in CHO-K1 cells (Kd=1200 nM). In contrast, clofilium and E4031 had a similar affinity in all three cell lines, whereas WAY 123,398 had no effect. Electrophysiological studies showed that SHSY5Y cells contained a HERG-like K+ current blocked by application of dofetilide to either side of the membrane. Block was faster when dofetilide was applied intracellularly. In contrast, HEK293 and CHO-K1 cells contained no such current, despite the presence of a partial cDNA for HERG in the former. That [3H]dofetilide is specific for I(Kr)/HERG may be questionable, as HEK293 and CHO-K1 cells contain no such functional K+ current.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dofetilide	Potassium voltage-gated channel subfamily H member 2	Protein	Humans	Yes	Inhibitor	Details