Dataset Information

Increased response to ??-adrenoreceptor stimulation augments inhibition of IKr in heart failure ventricular myocytes.

ABSTRACT:

Background

Increasing evidence indicates that the rapid component of delayed rectifier potassium current (I(Kr)) is modulated by ?- and ?-adrenergic stimulation. However, the role and mechanism regulating I(Kr) through ?(2)-adrenoreceptor (?-AR) stimulation in heart failure (HF) are unclear.

Methodology/principal findings

In the present study, we investigated the effects of fenoterol, a highly selective ?(2)-AR agonist, on I(Kr) in left ventricular myocytes obtained from control and guinea pigs with HF induced by descending aortic banding. I(Kr) was measured by using whole cell patch clamp technique. In control myocytes, superfusion of fenoterol (10 µM) caused a 17% decrease in I(Kr). In HF myocytes, the same concentration of fenoterol produced a significantly greater decrease (33%) in I(Kr). These effects were not modified by the incubation of myocytes with CGP-20712A, a ?(1)-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551, a ?(2)-AR antagonist. An inhibitory cAMP analog, Rp-cAMPS and PKA inhibitor significantly attenuated fenoterol-induced inhibition of I(Kr) in HF myocytes. Moreover, fenoterol markedly prolonged action potential durations at 90% (APD(90)) repolarization in HF ventricular myocytes.

Conclusions

The results indicate that inhibition of I(Kr) induced by ?(2)-AR stimulation is increased in HF. The inhibitory effect is likely to be mediated through a cAMP/PKA pathway in HF ventricular myocytes.

SUBMITTER: Wang H

PROVIDER: S-EPMC3460863 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Increased response to β₂-adrenoreceptor stimulation augments inhibition of IKr in heart failure ventricular myocytes.

Wang Hegui H Chen Yanhong Y Zhu Hongjun H Wang Sen S Zhang Xiwen X Xu Dongjie D Cao Kejiang K Zou Jiangang J

PloS one 20120928 9

<h4>Background</h4>Increasing evidence indicates that the rapid component of delayed rectifier potassium current (I(Kr)) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating I(Kr) through β(2)-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear.<h4>Methodology/principal findings</h4>In the present study, we investigated the effects of fenoterol, a highly selective β(2)-AR agonist, on I(Kr) in left ventricular myocytes obtained from control a ...[more]

PMID: 23029432

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