Discovery of Novel HCN4 Blockers with Unique Blocking Kinetics and Binding Properties.

ABSTRACT: The hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) channel underlies the pacemaker currents, called "If," in sinoatrial nodes (SANs), which regulate heart rhythm. Some HCN4 blockers such as ivabradine have been extensively studied for treating various heart diseases. Studies have shown that these blockers have diverse state dependencies and binding sites, suggesting the existence of potential chemical and functional diversity among HCN4 blockers. Here we report approaches for the identification of novel HCN4 blockers through a random screening campaign among 16,000 small-molecule compounds using an automated patch-clamp system. These molecules exhibited various blockade profiles, and their blocking kinetics and associating amino acids were determined by electrophysiological s

SUBMITTER: Nakashima K 

PROVIDER: S-EPMC8293762 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature