A team of researchers from the University of California, Irvine and the University of Copenhagen has found that two polyphenol compounds found in green and black teas, epicatechin gallate and epigallocatechin-3-gallate, selectively activate KCNQ5, a voltage-gated potassium channel expressed in vascular smooth muscle that regulates vascular tone.
Since its initial use in China over 4,000 years ago, tea — produced from the evergreen Camellia sinensis — has become one of the most commonly consumed beverages worldwide, second only to water.
Tea leaves contain polyphenols belonging to the catechin family — specifically epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin-3-gallate (EGCG).
The fermentation process of the leaves that results in the different tea varieties (green, oolong, and black) causes the oxidization of catechins, resulting in green tea containing a higher concentration of these compounds.
Tea catechins are known for their antioxidant properties and are thought to convey the therapeutic benefits of tea, with some studies showing anticancer and cardiovascular health benefits.
In new research, University of California, Irvine’s Professor Geoffrey Abbott and colleagues found that two catechin compounds, ECG and EGCG, each activate a specific type of ion channel protein named KCNQ5, which allows potassium ions to diffuse out of cells to reduce cellular excitability.
As KCNQ5 is found in the smooth muscle that lines blood vessels, its activation by tea catechins was also predicted to relax blood vessels.
“We found by using computer modeling and mutagenesis studies that specific catechins bind to the foot of the voltage sensor, which is the part of KCNQ5 that allows the channel to open in response to cellular excitation,” Professor Abbott said.
“This binding allows the channel to open much more easily and earlier in the cellular excitation process.”
In addition to its role in controlling vascular tone, KCNQ5 is expressed in various parts of the brain, where it regulates electrical activity and signaling between neurons.
Pathogenic KCNQ5 gene variants exist that impair its channel function and in doing so cause epileptic encephalopathy, a developmental disorder that is severely debilitating and causes frequent seizures.
Because catechins can cross the blood-brain barrier, discovery of their ability to activate KCNQ5 may suggest a future mechanism to fix broken KCNQ5 channels to ameliorate brain excitability disorders stemming from their dysfunction.
The scientists found that when black tea was directly applied to cells containing the KCNQ5 channel, the addition of milk prevented the beneficial KCNQ5-activating effects of tea.
“However, we don’t believe this means one needs to avoid milk when drinking tea to take advantage of the beneficial properties of tea,” Professor Abbott said.
“We are confident that the environment in the human stomach will separate the catechins from the proteins and other molecules in milk that would otherwise block catechins’ beneficial effects.”
The authors also found that warming green tea to 35 degrees Celsius alters its chemical composition in a way that renders it more effective at activating KCNQ5.
“Regardless of whether tea is consumed iced or hot, this temperature is achieved after tea is drunk, as human body temperature is about 37 degrees Celsius,” Professor Abbott said.
“Thus, simply by drinking tea we activate its beneficial, antihypertensive properties.”
The findings were published in the journal Cellular Physiology and Biochemistry.
Kaitlyn E. Redford et al. 2021. KCNQ5 Potassium Channel Activation Underlies Vasodilation by Tea. Cell Physiol Biochem 55 (S3): 46-64; doi: 10.33594/000000337
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