PHASE RESETTING AND ENTRAINMENT OF PACEMAKER ACTIVITY IN SINGLE SINUS NODAL CELLS
PHASE RESETTING AND ENTRAINMENT OF PACEMAKER ACTIVITY IN SINGLE SINUS NODAL CELLS
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DOI：
10.1161/01.res.68.4.1138
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发表时间：
1991-04-01
影响因子：
20.1
通讯作者：
JALIFE, J
中科院分区：
文献类型：
--
作者：
ANUMONWO, JMB;DELMAR, M;JALIFE, J
用计算机模拟兔窦房结细胞模型和分离的兔窦房结细胞的全细胞膜片钳(电流钳)技术，研究了单个起搏细胞的复相和夹带特性。细胞模型中的自发电活动用描述时间和电压依赖的膜电流的Hodgkin-Huxley类型方程重建。在模拟和实验中，使用单个亚阈值电流脉冲(去极化或超极化)来扫描细胞的自发周期。这种脉冲干扰了随后的放电，在起搏器周期中产生了暂时的相变，并使相位响应曲线的构建成为可能。在这些结果的基础上，我们研究了细胞的夹带特性。例如，重复脉冲的应用允许自发周期的相变，并在自发周期周围的基本周期长度范围内产生稳定的1：1夹带，或在基本周期长度值约为自发周期长度的一半时产生2：1的模式。在两个夹带区之间，观察到复杂的文克巴赫样图案(如5：4、4：3和3：2)。从理论上对分离细胞的实验数据进行了进一步的分析，结果表明，在细胞重复刺激过程中，相位重置行为的拓扑特征解释了实验观察到的模式。这是电耦合起搏器细胞、明显的结内传导和迷走神经反射性心率控制的首次演示。
The phase-resetting and entrainment properties of single pacemaker cells were studied using computer simulations in a model of the rabbit sinus nodal cell, as well as using the whole-cell patch-clamp (current-clamp) technique in isolated rabbit sinus nodal cells. Spontaneous electrical activity in the cell model was reconstructed using Hodgkin-Huxley-type equations describing time- and voltage-dependent membrane currents. In both simulations and experiments, single subthreshold current pulses (depolarizing or hyperpolarizing) were used to scan the spontaneous cycle of the cells. Such pulses perturbed the subsequent discharge, producing temporary phasic changes in pacemaker period, and enabled the construction of phase response curves. On the basis of these results, we studied entrainment characteristics of the cells. For example, application of repetitive pulses allowed for phasic changes in the spontaneous cycle and resulted in stable 1:1 entrainment at a range of basic cycle length around the spontaneous cycle, or a 2:1 pattern at basic cycle length values about half the spontaneous cycle length. Between the two entrainment zones, complex Wenckebach-like patterns (e.g., 5:4, 4:3, and 3:2) were observed. The experimental data from the isolated cell were further analyzed from a theoretical perspective, and the results showed that the topological characteristics of the phase-resetting behavior accounts for the experimentally observed patterns during repetitive stimulation of the cell. This first demonstration of phase electrically coupled pacemaker cells, apparent intranodal conduction, and reflex vagal control of heart rate.