A cellular mechanism contributing to postvagal tachycardia studied in isolated pacemaker cells from cat right atrium.
A cellular mechanism contributing to postvagal tachycardia studied in isolated pacemaker cells from cat right atrium.
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在猫右心房分离的起搏器细胞中研究了导致迷走后心动过速的细胞机制。
DOI：
10.1161/01.res.79.1.109
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发表时间：
1996
影响因子：
20.1
通讯作者：
Lipsius,SL
中科院分区：
文献类型：
--
作者：
Wang,YG;Lipsius,SL
迷走神经诱导的心跳抑制之后，迷走神经后心率增加，高于对照水平，迷走神经后心动过速。在本研究中，我们采用穿孔贴片/全细胞记录方法，研究了L钙电流(ICa，L)和超极化激活内向电流(IF)在乙酰胆碱(ACh)戒断引起的正性变时性反应中的作用。实验在分离的猫右心房窦房结(SAN)和潜伏期心房起搏(LAP)细胞上进行。撤除1μ/L ACh作用2分钟后，可引起ICa的反弹刺激，使SAN(33±4%)和LAP(50±6%)细胞均高于对照组。同样，撤除ACh(1μ摩尔/L)可引起SAN(21±4%)和LAP(20±6%)细胞IfE的反弹刺激。在ICA的反弹刺激中，L的峰值幅度在整个电压范围内都有所增加，激活的电压依赖性向更负的电压方向移动。动作电位记录显示，在ACh抑制后，停用ACh引起动作电位幅度的反弹增加(分别为+21±2%和+21±3%)，起搏周期长度缩短(分别为30±5%和44±5%)。CAMP依赖的蛋白激酶A抑制剂H-89(2μ/L)可阻断ACh戒断引起的ICa、L、IF、动作电位幅值的反弹增加和起搏周期长度的缩短。在IF阻断剂2 mmoL/L铯存在下，ACh停用引起的起搏周期长度的反弹缩短不变。我们的结论是，在SAN和LAP细胞中，撤除ACh主要通过cAMP介导的对ICa，L的反弹刺激引起正性变时性反应。这些发现首次证明了一种内在的细胞机制，该机制可能直接参与迷走神经后心动过速的非肾上腺素能成分。
Vagal nerve-induced inhibition of the heartbeat is followed by a postvagal increase in heart rate above control levels, postvagal tachycardia. In the present study, we used a perforated-patch/whole-cell recording method to determine the role of L-type Ca2+current (ICa,L) and the hyperpolarization-activated inward current (If) in the positive chronotropic response elicited by withdrawal of acetylcholine (ACh). Experiments were performed on sinoatrial node (SAN) and latent atrial pacemaker (LAP) cells isolated from cat right atrium. Withdrawal of a 2-minute exposure to 1 μmol/L ACh elicited a rebound stimulation of ICa,Lin both SAN (33±4%) and LAP (50±6%) cells above control. Similarly, withdrawal of ACh (1 μmol/L) elicited a rebound stimulation of Ifin both SAN (21±4%) and LAP (20±6%) cells. During the rebound stimulation of ICa,L, peak amplitude was increased throughout the voltage range, and the voltage dependence of activation was shifted to more negative voltages. Action potential recordings from both SAN and LAP cells showed that following ACh-induced inhibition, withdrawal of ACh elicited a concomitant rebound increase in action potential amplitude (+21±2% and +21±3%, respectively) and decrease in pacemaker cycle length (30±5% and 44±5%, respectively) compared with control. H-89 (2 μmol/L), an inhibitor of cAMP-dependent protein kinase A, abolished the rebound increase of ICa,L, If, action potential amplitude, and decrease in pacemaker cycle length elicited by withdrawal of ACh. In the presence of 2 mmol/L cesium, a blocker of If, the rebound decrease in pacemaker cycle length elicited by withdrawal of ACh was unchanged. We conclude that in SAN and LAP cells, withdrawal of ACh elicits a positive chronotropic response primarily through a cAMP-mediated rebound stimulation of ICa,L. These findings are the first demonstration of an intrinsic cellular mechanism that may contribute directly to the nonadrenergic component of postvagal tachycardia.