Long-QT mutations in KCNE1 modulate the 17ß-estradiol response of Kv7.1/KCNE1.
Sci Adv
; 9(11): eade7109, 2023 03 17.
Article
in En
| MEDLINE
| ID: mdl-36921038
ABSTRACT
Estradiol (17[Formula see text]-E2) is implicated in higher arrhythmia risk of women with congenital or acquired long-QT syndrome (LQTS) compared to men. However, the underlying mechanisms remain poorly understood, and little is known about the impact of LQTS-associated mutations. We show that 17[Formula see text]-E2 inhibits the human cardiac Kv7.1/KCNE1 channel expressed in Xenopus oocytes. We find that the 17[Formula see text]-E2 effect depends on the Kv7.1 to KCNE1 stoichiometry, and we reveal a critical function of the KCNE1 carboxyl terminus for the effect. LQTS-associated mutations in the KCNE1 carboxyl terminus show a range of responses to 17[Formula see text]-E2, from a wild-type like response to impaired or abolished response. Together, this study increases our understanding of the mechanistic basis for 17[Formula see text]-E2 inhibition of Kv7.1/KCNE1 and demonstrates mutation-dependent responses to 17[Formula see text]-E2. These findings suggest that the 17[Formula see text]-E2 effect on Kv7.1/KCNE1 might contribute to the higher arrhythmia risk of women, particularly in carriers with specific LQTS-associated mutations.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Long QT Syndrome
/
Potassium Channels, Voltage-Gated
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Sci Adv
Year:
2023
Document type:
Article
Affiliation country: