Free energy landscape remodeling of the cardiac pacemaker channel explains the molecular basis of familial sinus bradycardia.

ABSTRACT: The hyperpolarization-activated and cyclic nucleotide-modulated ion channel (HCN) drives the pacemaker activity in the heart, and its malfunction can result in heart disorders. One such disorder, familial sinus bradycardia, is caused by the S672R mutation in HCN, whose electrophysiological phenotypes include a negative shift in the channel activation voltage and an accelerated HCN deactivation. The outcomes of these changes are abnormally low resting heart rates. However, the molecular mechanism underlying these electrophysiological changes is currently not fully understood. Crystallographic investigations indicate that the S672R mutation causes limited changes in the structure of the HCN intracellular gating tetramer, but its effects on protein dynamics are unknown. Here, we utilize compa

SUBMITTER: Boulton S 

PROVIDER: S-EPMC5391768 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature