目的探讨槐果碱对心肌细胞动作电位(action potentials,AP)及离子电流的电生理效应。方法将豚鼠心脏快速取出后通过心电图记录心脏对槐果碱的应答;采用常规微电极技术对豚鼠乳头状肌或兔窦房结细胞快反应及慢反应动作电位进行记录,研究...目的探讨槐果碱对心肌细胞动作电位(action potentials,AP)及离子电流的电生理效应。方法将豚鼠心脏快速取出后通过心电图记录心脏对槐果碱的应答;采用常规微电极技术对豚鼠乳头状肌或兔窦房结细胞快反应及慢反应动作电位进行记录,研究槐果碱的相关效应;获取新生大鼠心室心肌细胞进行原代培养,采用膜片钳技术记录全细胞及单通道电流;采用穿孔膜片钳技术进行全细胞钙流记录。结果在异丙肾上腺素诱导后出现心动过速,而槐果碱(300μmol)加入后,心动过速或室颤现象消失,心电图提示出现正常心跳。对于豚鼠心室心肌细胞的快反应动作电位,槐果碱作用后,APD及动作电位的有效不应期延长,APA下降。对于窦房结的慢反应动作电位,槐果碱处理后,APA及Vmax均出现下降,且APD90也能够延长。结果显示槐果碱通过阻断I_(kr)而非I_(ks)实现对APD的延长。新生大鼠心室细胞的细胞电流实验结果显示10μmol/L槐果碱能够导致I_(Na)下降约18%。且槐果碱能够在全体细胞水平上降低慢内向电流,尾部电流(外向K+电流)也出现消失,相比于对照组,I_(CaL)在20 m V指令电位时,平均减少(33.2±11.7)%。结论槐果碱能够逆转异丙肾上腺素引起的心律失常,其作用机制为抑制Na离子、钙离子及钾离子电流。展开更多
The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range.A larger dynamic range indicates a greater probability of neuronal survival.In this study,the potential...The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range.A larger dynamic range indicates a greater probability of neuronal survival.In this study,the potential roles of adaptation mechanisms（ion currents） in modulating neuronal dynamic range were numerically investigated.Based on the adaptive exponential integrate-and-fire model,which includes two different adaptation mechanisms,i.e.subthreshold and suprathreshold（spike-triggered） adaptation,our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range.Specifically,subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range,while suprathreshold adaptation has little influence on the neuronal dynamic range.Moreover,when stochastic noise was introduced into the adaptation mechanisms,the dynamic range was apparently enhanced,regardless of what state the neuron was in,e.g.adaptive or non-adaptive.Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms.Additionally,noise was a non-ignorable factor,which could effectively modulate the neuronal dynamic range.展开更多
A trial electrophysiological heterogeneity, which plays an important role in the genesis and maintenance of atrial arrhythmia, is a major determinant of atrial reentrant arrhythmias. Recently, many studies on atrial f...A trial electrophysiological heterogeneity, which plays an important role in the genesis and maintenance of atrial arrhythmia, is a major determinant of atrial reentrant arrhythmias. Recently, many studies on atrial flutter have demonstrated the anatomic architecture in the right atrium plays an important role in the genesis of atrial reentry. The crista terminalis （CT） in the right atrium, which is a unique anatomic structure of the right atrium, provides an area for conduction block and delay, leading to initiation, maintenance, and termination of atrial arrhythmias. Catheter ablation of CT can successfully eliminate these atrial arrhythmias. These literatures contrast with limited knowledge of the basic electrophysiological properties of CT and how these promote arrhythmia generation. Compared to pectinate muscles （PM） and right atrial appendage （RAA）, CT have distinct electrophysiological properties related to different densities of several ionic currents, the transient outward current （Ito） and L-type Ca^2＋ current （Ica-L） underlie the bulk of the different densities of several ionic currents. Cardiac Ito and Ica-L play a major role in action potential repolarization. Ito is particularly important in early （phase 1） repolarization and influences the participation of other currents. It is generally believed that Ica-L plays an important role in the plateau phase of repolarization. However, the mechanisms for these ionic current differences are unknown. One possible is a difference in ion channel subunit expression, but virtually no data are available regarding ion-channel subunit expression in CT, PM, and RAA. The Kv4.3 channel underlies the bulk of the α-subunit of Ito in canine and human heart.展开更多
文摘目的探讨槐果碱对心肌细胞动作电位(action potentials,AP)及离子电流的电生理效应。方法将豚鼠心脏快速取出后通过心电图记录心脏对槐果碱的应答;采用常规微电极技术对豚鼠乳头状肌或兔窦房结细胞快反应及慢反应动作电位进行记录,研究槐果碱的相关效应;获取新生大鼠心室心肌细胞进行原代培养,采用膜片钳技术记录全细胞及单通道电流;采用穿孔膜片钳技术进行全细胞钙流记录。结果在异丙肾上腺素诱导后出现心动过速,而槐果碱(300μmol)加入后,心动过速或室颤现象消失,心电图提示出现正常心跳。对于豚鼠心室心肌细胞的快反应动作电位,槐果碱作用后,APD及动作电位的有效不应期延长,APA下降。对于窦房结的慢反应动作电位,槐果碱处理后,APA及Vmax均出现下降,且APD90也能够延长。结果显示槐果碱通过阻断I_(kr)而非I_(ks)实现对APD的延长。新生大鼠心室细胞的细胞电流实验结果显示10μmol/L槐果碱能够导致I_(Na)下降约18%。且槐果碱能够在全体细胞水平上降低慢内向电流,尾部电流(外向K+电流)也出现消失,相比于对照组,I_(CaL)在20 m V指令电位时,平均减少(33.2±11.7)%。结论槐果碱能够逆转异丙肾上腺素引起的心律失常,其作用机制为抑制Na离子、钙离子及钾离子电流。
基金supported by a grant from Beijing Municipal Commission of Science and Technology of China,No.Z151100000915070
文摘The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range.A larger dynamic range indicates a greater probability of neuronal survival.In this study,the potential roles of adaptation mechanisms（ion currents） in modulating neuronal dynamic range were numerically investigated.Based on the adaptive exponential integrate-and-fire model,which includes two different adaptation mechanisms,i.e.subthreshold and suprathreshold（spike-triggered） adaptation,our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range.Specifically,subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range,while suprathreshold adaptation has little influence on the neuronal dynamic range.Moreover,when stochastic noise was introduced into the adaptation mechanisms,the dynamic range was apparently enhanced,regardless of what state the neuron was in,e.g.adaptive or non-adaptive.Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms.Additionally,noise was a non-ignorable factor,which could effectively modulate the neuronal dynamic range.
基金This study was supported by a grant from the National Natural Science Foundation (No. 30470704).
文摘A trial electrophysiological heterogeneity, which plays an important role in the genesis and maintenance of atrial arrhythmia, is a major determinant of atrial reentrant arrhythmias. Recently, many studies on atrial flutter have demonstrated the anatomic architecture in the right atrium plays an important role in the genesis of atrial reentry. The crista terminalis （CT） in the right atrium, which is a unique anatomic structure of the right atrium, provides an area for conduction block and delay, leading to initiation, maintenance, and termination of atrial arrhythmias. Catheter ablation of CT can successfully eliminate these atrial arrhythmias. These literatures contrast with limited knowledge of the basic electrophysiological properties of CT and how these promote arrhythmia generation. Compared to pectinate muscles （PM） and right atrial appendage （RAA）, CT have distinct electrophysiological properties related to different densities of several ionic currents, the transient outward current （Ito） and L-type Ca^2＋ current （Ica-L） underlie the bulk of the different densities of several ionic currents. Cardiac Ito and Ica-L play a major role in action potential repolarization. Ito is particularly important in early （phase 1） repolarization and influences the participation of other currents. It is generally believed that Ica-L plays an important role in the plateau phase of repolarization. However, the mechanisms for these ionic current differences are unknown. One possible is a difference in ion channel subunit expression, but virtually no data are available regarding ion-channel subunit expression in CT, PM, and RAA. The Kv4.3 channel underlies the bulk of the α-subunit of Ito in canine and human heart.
