The molecular determinants of R-roscovitine block of hERG channels
Fig 1
Dose-response curve for R-roscovitine inhibition of WT hERG channels.
A) Skeletal formula of R-roscovitine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine. B) Pulse protocol (top) along with representative traces from a WT cell (bottom) exposed to the indicated R-roscovitine concentrations. Channels were activated with a 1-second step to +40 mV from -80 mV, and tail currents (◊) were elicited by a 1-second repolarization to -50 mV. The single 2-second episodic pulse was repeated for 3.44 minutes as the various concentrations were washed in and out of the gravity-fed perfusion system. C) Time-course of tail current inhibition (measured from ◊, in B) from a representative cell expressing WT hERG in the presence of the indicated R-roscovitine concentrations. D) Fractional block data were fitted with a Hill equation (see methods) to obtain the IC50 for WT hERG (196 ± 12 μM, n = 11). Error bars here and elsewhere represent standard errors.