• Nanion技术: 离子通道研究的智能工具

    Nanion技术: 离子通道研究的智能工具

  • CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

    CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

  • SURFE²R 96SE: 非标记高通量转运体筛选

    SURFE²R 96SE: 非标记高通量转运体筛选

  • 脂双层记录: Orbit产品系列

    脂双层记录: Orbit产品系列

我们的产品目录

SyncroPatch 384i

SyncroPatch 384i

Patchliner

Patchliner

Port-a-Patch

Port-a-Patch

Port-a-Patch mini

Port-a-Patch mini

CardioExcyte 96

CardioExcyte 96

FLEXcyte 96

FLEXcyte 96

SURFE²R 96SE

SURFE²R 96SE

SURFE²R N1

SURFE²R N1

Orbit 16

Orbit 16

Orbit Mini

Orbit Mini

Vesicle Prep Pro

Vesicle Prep Pro

2013 - Differential Effects of the β‐Adrenoceptor Blockers Carvedilol and Metoprolol on SQT1‐ and SQT2‐Mutant Channels

icon pap   Port-a-Patch publication in Journal of Cardiovascular Electrophysiology (2013)

Authors: 
Bodi I., Franke G., Pantulu N.D., Wu K., Perez-Feliz S., Bode C., Zehender M., Zur Hausen A., Brunner M., Odening K.

 

Journal: 
J Cardiovasc Electrophysiol (2013) 24(10):1163–1171


Abstract: 

Background:
N588K-KCNH2 and V307L-KCNQ1 mutations lead to a gain-of-function of IKr and IKs thus causing short-QT syndromes (SQT1, SQT2). Combined pharmacotherapies using K+-channel-blockers and β-blockers are effective in SQTS. Since β-blockers can block IKr and IKs, we aimed at determining carvedilol's and metoprolol's electrophysiological effects on N588K-KCNH2 and V307L-KCNQ1 channels.

Methods
Wild-type (WT)-KCNH2, WT-KCNQ1 and mutant N588K-KCNH2 and V307L-KCNQ1 channels were expressed in CHO-K1 or HEK-293T cells and IKs and IKr were recorded at baseline and during β-blocker exposure.

Results
Carvedilol (10 μM) reduced IKs tail in WT- and V307L-KCNQ1 by 36.5 ± 5% and 18.6 ± 9% (P < 0.05). IC50 values were 16.3 μM (WT) and 46.1 μM (V307L), indicating a 2.8-fold decrease in carvedilol's IKs-blocking potency in V307L-KCNQ1. Carvedilol's (1 μM) inhibition of the IKr tail was attenuated in N588K-KCNH2 (4.5 ± 3% vs 50.3 ± 4%, WT, P < 0.001) with IC50 values of 2.8 μM (WT) and 25.4 μM (N588K). Carvedilol's IKr end-pulse inhibition, however, was increased in N588K-KCNH2 (10 μM, 60.7 ± 6% vs 36.5 ± 5%, WT, P < 0.01).
Metoprolol (100 μM) reduced IKr end-pulse by 0.23 ± 3% (WT) and 74.1 ± 7% (N588K, P < 0.05), IKr tail by 32.9 ± 10% (WT) and 68.8 ± 7% (N588K, P < 0.05), and reduced IKs end-pulse by 18.3 ± 5% (WT) and 57.1 ± 11% (V307L, P < 0.05) and IKs tail by 3.3 ± 1% (WT) and 45.1 ± 13 % (V307L, P < 0.05), indicating an increased sensitivity to metoprolol in SQT mutated channels.

Conclusions
N588K-KCNH2 and V307L-KCNQ1 mutations decrease carvedilol's inhibition of the IKs or IKr tail but increase carvedilol's IKr end-pulse inhibition and metoprolol's inhibition of tail and end-pulse currents. These different effects on SQT1 and SQT2 mutated channels should be considered when using β-blocker therapy in SQTS patients.


Download here

返回总览

Nanion运营博客

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.