Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state.
Nat Commun
; 14(1): 7835, 2023 Dec 19.
Article
in En
| MEDLINE
| ID: mdl-38114487
ABSTRACT
Understanding voltage-gated sodium (Nav) channels is significant since they generate action potential. Nav channels consist of a pore domain (PD) and a voltage sensor domain (VSD). All resolved Nav structures in different gating states have VSDs that tightly interact with PDs; however, it is unclear whether VSDs attach to PDs during gating under physiological conditions. Here, we reconstituted three different voltage-dependent NavAb, which is cloned from Arcobacter butzleri, into a lipid membrane and observed their structural dynamics by high-speed atomic force microscopy on a sub-second timescale in the steady state. Surprisingly, VSDs dissociated from PDs in the mutant in the resting state and further dimerized to form cross-links between channels. This dimerization would occur at a realistic channel density, offering a potential explanation for the facilitation of positive cooperativity of channel activity in the rising phase of the action potential.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sodium
/
Ion Channel Gating
Language:
En
Journal:
Nat Commun
/
Nature communications
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2023
Type:
Article
Affiliation country:
Japan