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Updated: Jan 23, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
Published on: July 30, 2014
Disease-linked mutations alter the stoichiometries of HCN-KCNE2 complexes
Yoann Lussier1, Oliver Fürst1, Eva Fortea1
1Department of Pharmacology and Physiology, Université de Montréal, Montréal, Canada.
Abstract:
The four hyperpolarization-activated cylic-nucleotide gated (HCN) channel isoforms and their auxiliary subunit KCNE2 are important in the regulation of peripheral and central neuronal firing and the heartbeat. Disruption of their normal function has been implicated in cardiac arrhythmias, peripheral pain, and epilepsy. However, molecular details of the HCN-KCNE2 complexes are unknown. Using single-molecule subunit counting, we determined that the number of KCNE2 subunits in complex with the pore-forming subunits of human HCN channels differs with each HCN isoform and is dynamic with respect to concentration. These interactions can be altered by KCNE2 gene-variants with functional implications. The results provide an additional consideration necessary to understand heart rhythm, pain, and epileptic disorders.
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