Shumaker J M, Clark J W, Giles W R, Szabo G
Department of Electrical and Computer Engineering, Rice University, Houston, Texas 77251.
Biophys J. 1990 Mar;57(3):567-76. doi: 10.1016/S0006-3495(90)82572-8.
A model is formulated for characterizing the behavior of the acetylcholine (ACh)-sensitive K+ membrane channel (muscarinic channel) in bullfrog atrial myocytes. Parameters of the muscarinic current model are chosen in fit available data from the literature on bullfrog atrial myocytes (3, 4, 45). This model is subsequently incorporated into a large mathematical model of the bullfrog myocyte that is based on quantitative whole-cell voltage clamp data (40). Simulations are conducted on the active atrial cell model in bathing media containing ACh at different concentrations to explore the effect of this muscarinic channel on the electrical behavior of the myocyte. The model predicts a progressive shortening of the action potential with increasing [ACh], as well as an indirect influence of the muscarinic K+ current on the other membrane currents of the atrial cell. Interpretation of the simulation results provides suggestions for the probable mechanisms underlying the shortening of the action potential due to activity of the muscarinic channel. Specifically, the model predicts that with an increase in ACh concentration: (a) the outward muscarinic current, IK,ACh(t), increases in magnitude but shortens in duration; (b) the calcium current, ICa(t), may increase in magnitude, but when it does so it decreases in duration compared with the control conditions; (c) the intracellular Ca2+ concentration [Ca2+]i waveform during the action potential decreases in both magnitude and duration. Because the contractile activity of the cell is controlled by the [Ca2+]i waveform, the model predicts a decrease in contractile strength with an increase in ACh concentration in the bathing medium; i.e., a negative inotropic effect.
构建了一个模型来描述牛蛙心房肌细胞中乙酰胆碱（ACh）敏感钾离子膜通道（毒蕈碱型通道）的行为。毒蕈碱型电流模型的参数根据牛蛙心房肌细胞的文献数据（3, 4, 45）进行拟合选择。该模型随后被纳入基于全细胞电压钳定量数据的牛蛙心肌细胞大型数学模型（40）。在含有不同浓度ACh的浴液中，对活性心房细胞模型进行模拟，以探究该毒蕈碱型通道对心肌细胞电行为的影响。该模型预测，随着[ACh]增加，动作电位会逐渐缩短，并且毒蕈碱型钾电流对心房细胞的其他膜电流有间接影响。对模拟结果的解释为毒蕈碱型通道活性导致动作电位缩短的可能机制提供了建议。具体而言，该模型预测，随着ACh浓度增加：（a）外向毒蕈碱型电流IK,ACh(t)的幅度增加但持续时间缩短；（b）钙电流ICa(t)的幅度可能增加，但与对照条件相比，当其增加时持续时间会缩短；（c）动作电位期间细胞内Ca2+浓度[Ca2+]i波形的幅度和持续时间均减小。由于细胞的收缩活动由[Ca2+]i波形控制，该模型预测随着浴液中ACh浓度增加，收缩强度会降低；即负性变力作用。
