Delayed rectifier K⁺ current (I_Ks) is a key contributor to repolarization of action potentials. This study investigated the mechanisms underlying the adrenoceptor-induced potentiation of I_Ks in pulmonary vein cardiomyocytes (PVC). PVC were isolated from guinea pig pulmonary vein. The action potentials and I_Ks current were recorded using perforated and conventional whole-cell patch-clamp techniques. The expression of I_Ks was examined using immunocytochemistry and Western blotting. KCNQ1, a I_Ks pore-forming protein was detected as a signal band approximately 100 kDa in size, and its immunofluorescence signal was found to be mainly localized on the cell membrane. The I_Ks current in PVC was markedly enhanced by both β₁- and β₂-adrenoceptor stimulation with a negative voltage shift in the current activation, although the potentiation was more effectively induced by β₂-adrenoceptor stimulation than β₁-adrenoceptor stimulation. Both β-adrenoceptor-mediated increases in I_Ks were attenuated by treatment with the adenylyl cyclase (AC) inhibitor or protein kinase A (PKA) inhibitor. Furthermore, the I_Ks current was increased by α₁-adrenoceptor agonist but attenuated by the protein kinase C (PKC) inhibitor. PVC exhibited action potentials in normal Tyrode solution which was slightly reduced by HMR-1556 a selective I_Ks blocker. However, HMR-1556 markedly reduced the β-adrenoceptor-potentiated firing rate. The stimulatory effects of β- and α₁-adrenoceptor on I_Ks in PVC are mediated via the PKA and PKC signal pathways. HMR-1556 effectively reduced the firing rate under β-adrenoceptor activation, suggesting that the functional role of I_Ks might increase during sympathetic excitation under in vivo conditions.

延迟整流器 K ⁺电流 ( I _Ks ) 是动作电位复极化的关键因素。本研究调查了肾上腺素受体诱导的肺静脉心肌细胞 (PVC)中I _Ks增强的机制。PVC是从豚鼠肺静脉中分离出来的。使用穿孔和常规全细胞膜片钳技术记录动作电位和I _Ks电流。使用免疫细胞化学和蛋白质印迹检查I _Ks的表达。KCNQ1 ,a I _Ks成孔蛋白被检测为大小约为100 kDa的信号带，发现其免疫荧光信号主要位于细胞膜上。PVC 中的I _{Ks电流被 β 1} - 和 β ₂ - 肾上腺素能受体刺激显着增强，电流激活中的负电压偏移，尽管 β ₂ -肾上腺素能受体刺激比₁ -肾上腺素能受体刺激更有效地诱导了增强作用。用腺苷酸环化酶 (AC) 抑制剂或蛋白激酶 A (PKA) 抑制剂处理可减弱β-肾上腺素受体介导的I _Ks增加。此外，I _Ksα1-肾上腺素受体激动剂使电流增加，但被蛋白激酶C（PKC）抑制剂减弱。PVC 在正常 Tyrode 溶液中表现出动作电位，而 HMR-1556 是一种选择性I _Ks阻滞剂，略微降低了该动作电位。然而，HMR-1556 显着降低了 β-肾上腺素受体增强的放电率。_β-和α1-肾上腺素受体对PVC中I _Ks的刺激作用是通过PKA和PKC信号通路介导的。HMR-1556 有效降低了 β-肾上腺素受体激活下的放电率，表明I _{Ks的功能作用可能}在体内条件下的交感神经兴奋期间增加。