Functional Cross-Talk between the α1- and β1-Adrenergic Receptors Modulates the Rapidly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes

International Journal of Molecular Sciences

Di Xu¹  Sen Wang¹  Ting-Ting Wu¹  Xiao-Yan Wang²  Jin Qian² 

[1] Department of Geriatric Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;

关键词: adrenergic receptors;    potassium current;    cross-talk;    arrhythmia;   

DOI  :  10.3390/ijms150814220

来源: mdpi

【 摘 要 】

The rapidly activating delayed rectifier potassium current (I_Kr) plays a critical role in cardiac repolarization. Although I_Kr is known to be regulated by both α₁- and β₁-adrenergic receptors (ARs), the cross-talk and feedback mechanisms that dictate its response to α₁- and β₁-AR activation are not known. In the present study, I_Kr was recorded using the whole-cell patch-clamp technique. I_Kr amplitude was measured before and after the sequential application of selective adrenergic agonists targeting α₁- and β₁-ARs. Stimulation of either receptor alone (α₁-ARs using 1 μM phenylephrine (PE) or β₁-ARs using 10 μM xamoterol (Xamo)) reduced I_Kr by 0.22 ± 0.03 and 0.28 ± 0.01, respectively. The voltage-dependent activation curve of I_Kr shifted in the negative direction. The half-maximal activation voltage (V_0.5) was altered by −6.35 ± 1.53 and −1.95 ± 2.22 mV, respectively, with no major change in the slope factor (k). When myocytes were pretreated with Xamo, PE-induced reduction in I_Kr was markedly blunted and the corresponding change in V_0.5 was significantly altered. Similarly, when cells were pretreated with PE, Xamo-induced reduction of I_Kr was significantly attenuated. The present results demonstrate that functional cross-talk between α₁- and β₁-AR signaling regulates I_Kr. Such non-linear regulation may form a protective mechanism under excessive adrenergic stimulation.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.