DELAYED RECTIFIER CURRENT ASSAYS

SINGLE VENTRICULAR MYOCYTES

EFFECTS OF SOTALOL ON THE DELAYED RECTIFIER CURRENT I_Kr

Figure 1 Effects of sotalol on the delayed rectifier current I_Kr.

Figure 1 shows superimposed currents records elicited by a 40 ms and 400 ms step depolarisation to +40 mV in the absence (black) and presence (red) of sotalol (100 �
Membrane currents were recorded under standard conditions for the measurement of native I_K in single left ventricular myocytes using high resistance microelectrodes and the swirch-clamp technique.

Outward tail current elicited after a 40 ms step depolarisation which accurately reflects I_Kr is abolished by sotalol. 
However, tail currents elicited after a 400 ms step depolarisation which reflect both I_Kr and I_Ks  were only partially inhibited by sotalol. 

Figure 2  Effects of sotalol on I_Krand I_Ks.

Figure 2   Sotalol-induced prolongation of the action potential is mediated in part via inhibition of I_Kr.
These data (illustrated in Figure 2) show that the amplitude of the tail current activated after 40 ms, I_Kr, was significantly reduced by 75ॠby sotalol.  However, the amplitude of the tail current elicited after 400 ms, comprising both I_Ks and I_Kr, was only reduced by 39ॠreflecting the contribution of I_Kr to this current.

These data suggest the the effects of sotalol are mediated via and effects on I_Kr rather than on I_Ks.