Potassium channel blocker

Potassium channel blockers are agents which interfere with conduction through potassium channels.
Medical uses.
Arrhythmia.
Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic agents.
Mechanism.
Class III agents predominantly block the potassium channels, thereby prolonging repolarization. More specifically, their primary effect is on IKr.
Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become refractory).
Side effects.
These agents include a risk of torsades de pointes.
Anti-diabetics.
Sulfonylureas, such as gliclazide, are ATP-sensitive potassium channel blockers.
Other uses.
Dalfampridine, A potassium channel blocker has also been approved for use in the treatment of multiple sclerosis.
Reverse use dependence.
Potassium channel blockers exhibit reverse use-dependent prolongation of the action potential duration. Reverse use dependence is the effect where the efficacy of the drug is reduced after repeated use of the tissue. This contrasts with (ordinary) use dependence, where the efficacy of the drug is increased after repeated use of the tissue.
Reverse use dependence is relevant for potassium channel blockers used as class III antiarrhythmics. Reverse use dependent drugs that slow heart rate (such as quinidine) can be less effective at high heart rates. The refractoriness of the ventricular myocyte increases at lower heart rates. This increases the susceptibility of the myocardium to early Afterdepolarizations (EADs) at low heart rates. Antiarrhythmic agents that exhibit reverse use-dependence (such as quinidine) are more efficacious at preventing a tachyarrhythmia than converting someone into normal sinus rhythm. Because of the reverse use-dependence of class III agents, at low heart rates class III antiarrhythmic agents may paradoxically be more arrhythmogenic.
Drugs such as quinidine may be both reverse use dependent and use dependent.
Calcium-activated channel blockers.
Examples of calcium-activated channel blockers include:
Inwardly rectifying channel blockers.
Examples of inwardly rectifying channel blockers include:
ROMK (Kir1.1).
Nonselective: Ba2+, Cs+
Tandem pore domain channel blockers.
Examples of tandem pore domain channel blockers include:
Voltage-gated channel blockers.
Examples of voltage-gated channel blockers include: