Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.
Eur J Pharmacol
; 789: 98-108, 2016 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-27397430
ABSTRACT
In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 µΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300µM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30µM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30µM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell.
Palavras-chave
Atropine (PubChem CID: 174174); BAPTA-AM (PubChem CID: 2293); Barium Dichloride (PubChem CID: 25204); Cadmium Dichloride (PubChem CID: 24947); Dapoxetine (PubChem CID: 71353); Dimethyl sulfoxide (PubChem CID: 679); Flecainide (PubChem CID: 3356); HEK293 cells; Hesperetin; Hesperetin (PubChem CID: 72281); Human atrial myocytes; Ketanserin (PubChem CID: 3822); Kv1.5 potassium channel; Maleimide (PubChem CID: 10935); Nicardipine (PubChem CID: 4474); Ultra-rapid delayed rectifier K(+) current; Whole-cell patch-clamp
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potássio
/
Miócitos Cardíacos
/
Canal de Potássio Kv1.5
/
Fenômenos Eletrofisiológicos
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Átrios do Coração
/
Hesperidina
Limite:
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2016
Tipo de documento:
Article