The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator

Autor: Geoffrey W. Abbott, Kaitlyn E Redford
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Protein Structure
Patch-Clamp Techniques
Physiology
Rutin
Potassium
Flavonoid
Medicine (miscellaneous)
chemistry.chemical_element
Article
General Biochemistry
Genetics and Molecular Biology
KCNQ3 Potassium Channel
Kv channel
Xenopus laevis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
food
Complementary and Integrative Health
Animals
KCNQ2 Potassium Channel
heterocyclic compounds
lcsh:QH301-705.5
Nutrition
Pharmacology
chemistry.chemical_classification
Binding Sites
Molecular medicine
KCNQ Potassium Channels
Plant Extracts
Capparis spinosa
fungi
food and beverages
Potassium channel activator
food.food
Protein Structure
Tertiary
Capparis
030104 developmental biology
chemistry
Biochemistry
lcsh:Biology (General)
Oocytes
Natural source
Quercetin
General Agricultural and Biological Sciences
Tertiary
030217 neurology & neurosurgery
KCNQ4
Zdroj: Communications Biology, Vol 3, Iss 1, Pp 1-15 (2020)
Communications biology, vol 3, iss 1
Communications Biology
ISSN: 2399-3642
Popis: Many commonly consumed plants are used as folk medicines, often with unclear molecular mechanisms. Recent studies uncovered the ubiquitous and influential KCNQ family of voltage-gated potassium (Kv) channels as a therapeutic target for several medicinal plant compounds. Capers - immature flower buds of Capparis spinosa - have been consumed for food and medicinal purposes for millennia. Here, we show that caper extract hyperpolarizes cells expressing KCNQ1 or KCNQ2/3 Kv channels. Capers are the richest known natural source of quercetin, the most consumed dietary flavonoid. Quercetin potentiated KCNQ1/KCNE1, KCNQ2/3 and KCNQ4 currents but, unusually, not KCNQ5. Strikingly, quercetin augmented both activation and inactivation of KCNQ1, via a unique KCNQ activation mechanism involving sites atop the voltage sensor and in the pore. The findings uncover a novel potential molecular basis for therapeutic effects of quercetin-rich foods and a new chemical space for atypical modes of KCNQ channel modulation.
Kaitlyn E. Redford and Geoffrey W. Abbott show that quercetin, a flavonoid highly expressed in capers, potentiates KCNQ currents to varying degrees depending on the subunit composition of the channel complex. By combining in silico docking, mutagenesis, and electrophysiology they show that this flavonoid can bind KCNQ channels atop the voltage sensor and within the pore module, highlighting an atypical mode of channel modulation.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje