KCNQ5 Potassium Channel Activation Underlies Vasodilation by Tea

Abstract

BACKGROUND/AIMS: Tea, produced from the evergreen Camellia sinensis, has reported therapeutic properties against multiple pathologies, including hypertension. Although some studies validate the health benefits of tea, few have investigated the molecular mechanisms of action. The KCNQ5 voltage-gated potassium channel contributes to vascular smooth muscle tone and neuronal M-current regulation. METHODS: We applied electrophysiology, myography, mass spectrometry and in silico docking to determine effects and their underlying molecular mechanisms of tea and its components on KCNQ channels and arterial tone. RESULTS: A 1% green tea extract (GTE) hyperpolarized cells by augmenting KCNQ5 activity >20-fold at resting potential; similar effects of black tea were inhibited by milk. In contrast, GTE had lesser effects on KCNQ2/Q3 and inhibited KCNQ1/E1. Tea polyphenols epicatechin gallate (ECG) and epigallocatechin-3-gallate (EGCG), but not epicatechin or epigallocatechin, isoform-selectively hyperpolarized KCNQ5 activation voltage dependence. In silico docking and mutagenesis revealed that activation by ECG requires KCNQ5-R212, at the voltage sensor foot. Strikingly, ECG and EGCG but not epicatechin KCNQ-dependently relaxed rat mesenteric arteries. CONCLUSION: KCNQ5 activation contributes to vasodilation by tea; ECG and EGCG are candidates for future anti-hypertensive drug development.

Green Tea Catechins, (−)‐Catechin Gallate, and (−)‐Gallocatechin Gallate are Potent Inhibitors of ABA‐Induced Stomatal Closure

“…[ 27 ] We speculated that water‐soluble compounds present in green tea might affect these plasma membrane‐located K + channels. Catechin derivatives contained in green tea are known to regulate ion transport activities of Shaker ‐type K + channels [ 20 , 21 , 22 ] by binding to the gap site between S4 and S5, [ 28 ] and Ca 2+ channels. [ 29 , 30 ] Prior to this test on plant channels, we tested whether green tea directly affects the activity of animal K + channels using two‐electrode voltage clamp recordings of Xenopus oocytes ( Figure 2 ).…”

“…This suggested that catechins had some affinity to Shaker ‐type ion channels, which was consistent with a previous report. [ 28 ] We performed the same measurement on Shaker ‐type K + channels, KAT1 and KAT2, which function in the plasma membrane of Arabidopsis guard cells [ 34 ] (Figure 2 ). The addition of green tea to the bath buffer decreased KAT1 and KAT2‐mediated currents by more than 40%, compared to the buffer without green tea (Figure 2A,B ).…”

“…These results indicated that some ingredients of green tea inhibited the activity of Shaker ‐type K + channels. According to the model of Shaker ‐type K + channels, KCNQ5 with ECG, [ 28 ] catechins might be associated with S4‐S5 of Arabidopsis Shaker ‐type ion channels.…”

“…[ 30 ] KCNQ5 is also activated by EGC as well as EGCG, leading to the conclusion that EGC interacts with the connecting sites between the voltage sensor domain of S4 and S5. [ 28 ] Moreover, this position serves as binding sites of other small chemicals, that is , γ ‐aminobutyric acid (GABA). [ 51 ] Analogous catechin derivatives, CG and GCG are classified as minor catechins in green tea, and their physiological impact on animals and plants is unclear.…”

GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease

“…One example is the ester of epigallocatechin and gallic acid, ( −)-Epigallocatechin-3-Gallate (EGCG), the most bioactive polyphenol found in green tea extract. EGCG significantly increased mRNA expression of the key autophagy adaptor proteins NDP52 and p62 and enhanced the clearance of AD-relevant phosphorylated tau species in primary neurons [ 145 ], as well as improving cerebrovascular tone [ 146 ]. EGCG also activated autophagic pathways by inducing Sirt1, exerting protective effects against human prion protein-induced neurotoxicity [ 69 ].…”