Tissue-specific effects of acetylcholine in the canine heart
Tissue-specific effects of acetylcholine in the canine heart
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DOI：
10.1152/ajpheart.00029.2013
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发表时间：
2013-07-01
影响因子：
4.8
通讯作者：
Cordeiro, Jonathan M.
中科院分区：
文献类型：
--
作者：
Calloe, Kirstine;Goodrow, Robert;Cordeiro, Jonathan M.
迷走神经释放的乙酰胆碱 (ACh) 会减慢心率和房室传导。 ACh 刺激多种受体和通道，包括内向整流电流 [ACh 依赖性 K+ 电流 (I-K,I- ACh)]。乙酰胆碱对心室的影响仍有争议。我们比较了乙酰胆碱对犬心房、浦肯野和心室组织动作电位以及分离细胞中离子电流的影响。从心室切片、浦肯野纤维和动脉灌注心房制剂记录动作电位。在电压钳条件下记录全细胞电流，并在分离的细胞上测定卸载的细胞缩短。测试了 ACh (1-10 μM) 以及 ACh 加特硫平（一种 I-K,I- ACh 特异性毒素）的效果。在心房组织中，ACh 使膜电位超极化并缩短动作电位持续时间 (APD)。在浦肯野和心室组织中，没有观察到乙酰胆碱的显着影响。向心房细胞添加ACh激活了大的内向整流电流（从-3.5+/-0.7到-23.7+/-4.7pA/pF），该电流被特硫平消除。在其他细胞类型中未观察到该电流。 ACh 作用后，在心房、心内膜和心外膜中观察到 Ca2+ 电流 (I-Ca) 的轻微抑制。 I-Ca 抑制随着起搏速度的加快而增加。在 400 ms 的基本周期长度下，ACh (1 μM) 将 I-Ca 降低至对照的 68%。总之，I-K,I-ACh 在心房中高度表达，而在浦肯野细胞、心内膜和心外膜细胞中可忽略不计/不存在。在所有心脏组织中，ACh 都会引起 I-Ca 的速率依赖性抑制。
Acetylcholine (ACh) release from the vagus nerve slows heart rate and atrioventricular conduction. ACh stimulates a variety of receptors and channels, including an inward rectifying current [ACh-dependent K+ current (I-K,I- ACh)]. The effect of ACh in the ventricle is still debated. We compared the effect of ACh on action potentials in canine atria, Purkinje, and ventricular tissue as well as on ionic currents in isolated cells. Action potentials were recorded from ventricular slices, Purkinje fibers, and arterially perfused atrial preparations. Whole cell currents were recorded under voltage-clamp conditions, and unloaded cell shortening was determined on isolated cells. The effect of ACh (1-10 mu M) as well as ACh plus tertiapin, an I-K,I- ACh-specific toxin, was tested. In atrial tissue, ACh hyperpolarized the membrane potential and shortened the action potential duration (APD). In Purkinje and ventricular tissues, no significant effect of ACh was observed. Addition of ACh to atrial cells activated a large inward rectifying current (from -3.5 +/- 0.7 to -23.7 +/- 4.7 pA/pF) that was abolished by tertiapin. This current was not observed in other cell types. A small inhibition of Ca2+ current (I-Ca) was observed in the atria, endocardium, and epicardium after ACh. I-Ca inhibition increased at faster pacing rates. At a basic cycle length of 400 ms, ACh (1 mu M) reduced I-Ca to 68% of control. In conclusion, I-K,I- ACh is highly expressed in atria and is negligible/absent in Purkinje, endocardial, and epicardial cells. In all cardiac tissues, ACh caused rate-dependent inhibition of I-Ca.