Targeting the I_Ks Channel PKA Phosphorylation Axis to Restore Its Function in High-Risk LQT1 Variants.

ABSTRACT:

Background

The KCNQ1+KCNE1 (I_Ks) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the I_Ks channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between I_Ks channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear.

Methods

Regular patch clamp and voltage c

SUBMITTER: Zhong L 

PROVIDER: S-EPMC11392204 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature