Atomistic mechanisms of the regulation of small-conductance Ca²⁺-activated K⁺ channel (SK2) by PIP2.

ABSTRACT: Small-conductance Ca²⁺-activated K⁺ channels (SK, K_Ca2) are gated solely by intracellular microdomain Ca²⁺. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca²⁺ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate (PIP2) coordinates with CaM in regulating SK channels. However, the roles and mechanisms of PIP2 in regulating SK channels in cardiomyocytes remain unknown. Here, optogenetics, magnetic nanoparticles, combined with Rosetta structural modeling, and molecular dynamics (MD) simulations revealed the atomistic mechanisms of how PIP2 works in c

SUBMITTER: Woltz RL 

PROVIDER: S-EPMC11441529 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature