CAJ | 학술논문

目的研究心脏M3受体/M3受体介导的钾通道与心律失常的关系,寻找抗心律失常药物的新靶点.方法分别以结扎大鼠左冠状动脉前降支所致急性心律失常模型和膜片钳技术为基础,观察M3受体的干预作用及作用机制.结果M3受体阻断剂4DAMP(4-diphenylacetoxy-N-methylpiperidine-methiodide)加重结扎大鼠冠状动脉前降支所致心律失常,而M3受体激动剂胆碱能明显对抗其作用.其他亚型受体阻断剂,M1受体阴断剂(prienzepine)、M2受体阻断剂(methotramine)和M4受体阻断剂(tropicamide)对结扎大鼠左冠状动脉前降支所致急性心律失常无影响.在膜片钳实验中发现,胆碱可激活一种延迟整流钾电流(IKM3),此电流可被M3受体阻断剂4DAMP明显抑制.而M1,M2和M4受体阻断挤对胆碱介导的电流无作用.M3受体/IKM3可能是抗心律失常新靶点.
목적연구심장M3수체/M3수체개도적갑통도여심률실상적관계,심조항심률실상약물적신파점.방법분별이결찰대서좌관상동맥전강지소치급성심률실상모형화막편겸기술위기출,관찰M3수체적간예작용급작용궤제.결과M3수체조단제4DAMP(4-diphenylacetoxy-N-methylpiperidine-methiodide)가중결찰대서관상동맥전강지소치심률실상,이M3수체격동제담감능명현대항기작용.기타아형수체조단제,M1수체음단제(prienzepine)、M2수체조단제(methotramine)화M4수체조단제(tropicamide)대결찰대서좌관상동맥전강지소치급성심률실상무영향.재막편겸실험중발현,담감가격활일충연지정류갑전류(IKM3),차전류가피M3수체조단제4DAMP명현억제.이M1,M2화M4수체조단제대담감개도적전류무작용.M3수체/IKM3가능시항심률실상신파점.
Aim To investigate the relationship between M3-R/IKM3 and arrhythmia in order to find a new target for antiarrhythmic agents. Methods Using the acute ischemic model of rats and patch-clamp techniques, the effects of the M3 receptor on the occurrence of arrhythmias and its possible mechanisms were studied. Results In acute ischemic model of rats, the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine-methiodide (4DAMP) increased the occurrence of arrhythmias, and the M3 receptor agonist choline suppressed the onset and the development of arrhythmias (P ＜ 0.01 ). No change was observed after treatment with other receptor antagonists (M1, M2, and M4 ). With patch-clamp techniques, it was found that choline induced K+ current could be inhibited by 4DAMP. Antagonists toward M1 , M2, and M4 receptors all failed to alter the current. Conclusion Choline modulates the cellular electrical properties of the heart, probably by activating a K + current via stimulation of the M3 receptor. M3-R/IKM3 may act as a new target for antiarrhythmic agents.