Wanted: Class VI Antiarrhythmic Drug Action; New Start for a Rational Drug Therapy

Figures

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  Figure 1:. Schematic showing targets of Class VI antiarrhythmic drug action: Roscovitine, which reduces the pedestal current (downward green arrow); Gabapentinoids, which shift the steady-state activation in the depolarizing direction (rightward green arrow); potential sites of gating modifier drugs (currently no examples), which shift the steady-state inactivation curve in the hyperpolarizing direction (leftward green arrow). Similar shifts in the INa are also potential targets for AADs, however at the present no such drugs are available (see text for further discussion). Note that Class IV drugs (verapamil & diltiazem) reduce peak ICa-L (red arrow) (Figure modified from [17]).

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  Figure 2:. Enhanced late ICa-L in Timothy syndrome in iPSC-derived cardiomyocytes and its selective suppression by Roscovitine (Ros) without affecting peak ICa-L (modified from [29]).

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  Figure 3:. Schematic showing the components of the late ICa-L, the window and pedestal current.

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  Figure 4:. Selective suppression of the INa-L by GS-458967 in isolated cardiomyocytes (modified from [43]).