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Updated: Oct 2, 2025

Recapitulation of an Ion Channel IV Curve Using Frequency Components
Published on: February 8, 2011
Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel
Flavio Costa1, Carlo Guardiani1, Alberto Giacomello2
1Dipartimento di Ingegneria Meccanica e Aerospaziale, Sapienza Università di Roma, Via Eudossiana 18, 00184, Rome, Italy.
Abstract:
The elusive activation/deactivation mechanism of hERG is investigated, a voltage-gated potassium channel involved in severe inherited and drug-induced cardiac channelopathies, including the Long QT Syndrome. Firstly, the available structural data are integrated by providing a homology model for the closed state of the channel. Secondly, molecular dynamics combined with a network analysis revealed two distinct pathways coupling the voltage sensor domain with the pore domain. Interestingly, some LQTS-related mutations known to impair the activation/deactivation mechanism are distributed along the identified pathways, which thus suggests a microscopic interpretation of their role. Split channels simulations clarify a surprising feature of this channel, which is still able to gate when a cut is introduced between the voltage sensor domain and the neighboring helix S5. In summary, the presented results suggest possible activation/deactivation mechanisms of non-domain-swapped potassium channels that may aid in biomedical applications.
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