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DELAYED RECTIFIER CURRENT ASSAYS
SINGLE VENTRICULAR MYOCYTES
EFFECTS OF DOFETILIDE ON THE DELAYED RECTIFIER
CURRENT IKr
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Figure 1
Effects of dofetilide
on the delayed rectifier current IKr.
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Figure 1
shows an example of typical IKr tail currents recorded by scientists at
OCP, under our
standard whole-cell patch-clamp conditions for
the measurement of native IK in single
left ventricular myocytes.
Figure 1 shows superimposed current records elicited by a
40 ms step depolarisation to +40 mV in the absence (black) and
presence (red) of dofetilide (1 鮍
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Figure 2
Time course for the effect of dofetilide on the amplitude of IKr .
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Figure 2 shows that under these conditions tail
current amplitude (denoted by black symbols) is stable over the
5 minute control recording period. Application of
dofetilide (1 頣aused a time dependent decrease in the outward tail current consistent with complete
block of IKr.
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Figure 3
Determination of the IC50
of dofetilide on IKr measured in single ventricular myocytes.
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Figure 3 shows the percentage decrease in the peak
amplitude of IKr plotted as a function
of concentration of dofetilide.
The left hand panel shows the data points taken from individual experiments.
The right hand panel shoes
mean孠data for these experiment. These data points can be fit by
a sigmoid curve (logistic function) which produces and IC50 value of
13�
This value for the potency of dofetilide to block IKr in
native ventricular myocytes is similar to values reported in the literature
for the effect of E-4031 on hERG channels.
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