Home
Resources
Publications
Characterization and Molecular Basis for the Block of Kv1.3 Channels Induced by Carvedilol in HEK293 Cells

Characterization and Molecular Basis for the Block of Kv1.3 Channels Induced by Carvedilol in HEK293 Cells

Jin-Feng Yang, Neng Cheng, Sheng Ren, Xiang-Ming Liu, Xian-Tao Li

Eur J Pharmacol. 2018 Sep 5;834:206-212.

PMID: 30016664

Abstract:

Carvedilol is a non-selective β-adrenoreceptor antagonist and exhibits a wide range of biological activities. The voltage-gated K+ (Kv) channel is one of the target ion channels of this compound. The rapidly activating Kv1.3 channel is expressed in several different tissues and plays an important role in the regulation of physiological functions, including cell proliferation and apoptosis. However, little is known about the possible action of carvedilol on Kv1.3 currents. Using the whole-cell configuration of the patch-clamp technique, we have revealed that exposure to carvedilol produced a concentration-dependent blocking of Kv1.3 channels heterologously expressed in HEK293 cells, with an IC50 value of 9.7 μM. This chemical decelerated the deactivation tail current of Kv1.3 currents, resulting in a tail crossover phenomenon. In addition, carvedilol generated a markedly hyperpolarizing shift (20 mV) of the inactivation curve, but failed to affect the activation curve. Mutagenesis experiments of Kv1.3 channels identified G427 and H451, two related sites of TEA block, as important residues for carvedilol-mediated blocking. The present results suggest that carvedilol acts directly on Kv1.3 currents by inducing closed- and open-channel block and helps to elucidate the mechanisms of action of this compound on Kv channels.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1198090731-B	Carvedilol Related Compound A		1198090-73-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: