DELAYED RECTIFIER CURRENT ASSAYS

SINGLE VENTRICULAR MYOCYTES

EFFECTS OF DOFETILIDE ON THE DELAYED RECTIFIER CURRENT IKr

Figure 1 Effects of dofetilide on the delayed rectifier current IKr.

Figure 1 shows an example of typical IKr tail currents recorded by scientists at OCP recorded under our standard conditions for the measurement of native IK in single left ventricular myocytes using high resistance microelectrodes and the swirch-clamp technique.
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 (100 nM).
Outward tail currents elicited on repolarisation to the holding potential (-40 mV) accurately reflect activation of IKr. 
These data show that application of dofetilide (3 minutes) abolished the outward tail current consistent with complete inhibition of IKr.

 
 

Figure 2 Effects of dofetilide on IKrand IKs.

 
 

Figure 2  shows that Dofetilide-induced prolongation of the action potential is mediated in part via inhibition of IKr.
These data (illustrated in Figure 2) show that the amplitude of the tail current activated after 40 ms, IKr, was significantly reduced by 95ॠby dofetilide.  However, the amplitude of the tail current elicited after 400 ms, comprising both IKr and non blocked IKs, was only reduced by 43ॠ reflecting the contribution of IKr to this current.
These data suggest the the effects of dofetilide are mediated via and effects on IKr rather than on IKs.

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