The fully activated open state of KCNQ1 controls the cardiac "fight-or-flight" response.

ABSTRACT: The cardiac KCNQ1 + KCNE1 (I_Ks) channel regulates heart rhythm under both normal and stress conditions. Under stress, the β-adrenergic stimulation elevates the intracellular cyclic adenosine monophosphate (cAMP) level, leading to KCNQ1 phosphorylation by protein kinase A and increased I_Ks, which shortens action potentials to adapt to accelerated heart rate. An impaired response to the β-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1). However, the underlying mechanism of β-adrenergic stimulation of I_Ks remains unclear, impeding the development of new therapeutics. Here, we find that the unique properties of KCNQ1 channel gating with two distinct open states

SUBMITTER: Hou P 

PROVIDER: S-EPMC11492796 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature