DELAYED RECTIFIER CURRENT ASSAYS

SINGLE VENTRICULAR MYOCYTES

EFFECTS OF E-4031 ON THE DELAYED RECTIFIER CURRENT IKr

Figure 1  Effects of E-4031 on the delayed rectifier current IKr.

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.

Outward tail currents elicited on repolarisation to the holding potential (-40 mV) accurately reflect activation of IKr.

Figure 1 shows superimposed current records elicited by a 40 ms step depolarisation to +40 mV in the absence (black) and presence (red) of E-4031 (3 鮍

 

Figure 2   Time course for the effect of E-4031 on the amplitude of IKr .

 
 

Figure 2  shows that under these conditions tail current amplitude (denoted by black symbols) is stable over the control recording period. Application of E-4031 (3 যr 3 minutes) caused a time dependent decrease in the outward tail current consistent with complete block of IKr.


 

Figure 3   Determination of the IC50 of E-4031 on IKr measured in single ventricular myocytes.


Figure 3   shows the percentage decrease in the peak amplitude of IKr plotted as a function concentration of E-4031.

The left hand panel shows the data points taken from individual experiments showing the spread of these data.

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 42�

This value for the potency of E-4031 to block IKr in native ventricular myocytes is similar to values reported in the literature for the effect of E-4031 on hERG channels.


 

 
  All data 㯰yright to OCP Ltd. 2006. All Rights Reserved. Design by OCP