IKs

IKs, the slow delayed rectifier potassium current, is a voltage-gated potassium current in cardiac myocytes that contributes to repolarization of the cardiac action potential. It activates gradually after depolarization and becomes more significant at higher heart rates, aiding rate-dependent shortening of the action potential duration during sympathetic stimulation.

Molecularly, IKs channels form by the pore-forming KCNQ1 (Kv7.1) α-subunits assembling into tetramers and associating with the auxiliary KCNE1 (minK) subunit, which modulates kinetics and voltage dependence. The presence of KCNE1 alters activation timing, current density, and pharmacology. The current is relatively small at slow heart rates but increases with depolarization and adrenergic drive.

Regulation involves sympathetic signaling: beta-adrenergic stimulation activates PKA, leading to phosphorylation of the channel complex and its accessory proteins. This phosphorylation shifts the voltage dependence and accelerates activation, boosting IKs to shorten the action potential during tachycardia.

Clinical relevance centers on dysfunction of IKs, typically from mutations in KCNQ1 (associated with long QT syndrome type 1) or KCNE1 (associated with long QT syndrome type 5). Such defects prolong repolarization and increase the risk of torsades de pointes and syncope. Management includes beta-blockers and avoidance of drugs that prolong QT, with genetic testing and, in some cases, device therapy as part of overall care.