Effects of (-)-epigallocatechin-3-gallate, the main component of green tea, on the cloned rat brain Kv1.5 potassium channels

Citation
Bh. Choi et al., Effects of (-)-epigallocatechin-3-gallate, the main component of green tea, on the cloned rat brain Kv1.5 potassium channels, BIOCH PHARM, 62(5), 2001, pp. 527-535
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
5
Year of publication
2001
Pages
527 - 535
Database
ISI
SICI code
0006-2952(20010901)62:5<527:EO(TMC>2.0.ZU;2-3
Abstract
The interaction of (-)-epigallocatechin-3-gallate (EGCG), the main componen t of green tea (Camellia sinensis), with rat brain Kv1.5 channels (rKv1.5) stably expressed in Chinese hamster ovary (CHO) cells was investigated usin g the whole-cell patch-clamp technique. EGCG inhibited rKv1.5 currents at 50 mV in a concentration-dependent manner, with an IC50 of 101.2 +/- 6.2 mu M. Pretreatment with protein tyrosine kinase (PTK) inhibitors (10 muM genis tein, 100 muM AG1296), a tyrosine phosphatase inhibitor (500 muM sodium ort hovanadate), or a protein kinase C (PKC) inhibitor (10 muM chelerythrine) d id not block the inhibitory effect of EGCG on rKv1.5. The inhibition of rKv 1.5 by EGCG displayed voltage-independence over the full activation voltage range positive to +10 mV. EGCG had no effect on the midpoint potential or the slope factor for steady-state activation and inactivation. EGCG did not affect the ion selectivity of rKv1.5. The activation (at +50 mV) kinetics was significantly slowed by EGCG. During repolarization (at -40 mV), EGCG a lso slowed the deactivation of the tail currents, resulting in a crossover phenomenon. Reversal of inhibition was detected by the application of repet itive depolarizing pulses and of identical double pulses, especially during the early part of the activating pulse, in the presence of EGCG. EGCG-indu ced inhibition of rKv1.5 showed identical affinity between EGCG and the mul tiple closed states of rKv1.5. These results suggest that EGCG interacts di rectly with rKv1.5 channels. Furthermore, by analyzing the kinetics of the interaction between EGCG and rKv1.5, we conclude that the inhibition of rKv 1.5 channels by EGCG includes at least two effects: EGCG preferentially bin ds to the channel in the closed state, and blocks the channel by pore occlu sion while depolarization is maintained. (C) 2001 Elsevier Science Inc. All rights reserved.