KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines.
Proc Natl Acad Sci U S A
; 116(42): 21236-21245, 2019 10 15.
Article
em En
| MEDLINE
| ID: mdl-31570602
ABSTRACT
Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio KCNQ
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article