Noncanonical electromechanical coupling paths in cardiac hERG potassium channel.
Nat Commun
; 14(1): 1110, 2023 02 27.
Article
em En
| MEDLINE
| ID: mdl-36849440
ABSTRACT
Voltage-gated potassium channels are involved in many physiological processes such as nerve impulse transmission, the heartbeat, and muscle contraction. However, for many of them the molecular determinants of the gating mechanism remain elusive. Here, using a combination of theoretical and experimental approaches, we address this problem focusing on the cardiac hERG potassium channel. Network analysis of molecular dynamics trajectories reveals the presence of a kinematic chain of residues that couples the voltage sensor domain to the pore domain and involves the S4/S1 and S1/S5 subunit interfaces. Mutagenesis experiments confirm the role of these residues and interfaces in the activation and inactivation mechanisms. Our findings demonstrate the presence of an electromechanical transduction path crucial for the non-domain-swapped hERG channel gating that resembles the noncanonical path identified in domain-swapped K+ channels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio de Abertura Dependente da Tensão da Membrana
/
Contração Muscular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2023
Tipo de documento:
Article