乙酰胆碱诱发的豚鼠心室肌反跳作用研究

观察乙酰胆碱 (ACh)诱发的豚鼠心室肌肌力及钙电流的反跳作用 ,并探讨其作用机制。采用豚鼠离体左室乳头肌观察 1μmol/LACh单独对心室肌收缩力 (Fc)的影响及在 10nmol/L异丙肾上腺素 (Iso)存在时对Fc的影响 ,并应用膜片钳全细胞记录方法分别观察 1μmol/LACh和 1μmol/LACh +10nmol/LIso及迅速洗脱ACh对豚鼠心室肌细胞L型钙通道电流 (ICa L)的影响。结果 :1μmol/LACh对心室肌Fc有直接抑制作用 ,抑制率为 30 .8%± 10 .7%(P <0 .0 5 ) ,而快速洗脱ACh后 ,Fc反跳性增强了 2 5 .5 %± 10 .3% (n =7,P <0 .0 1)。而在应用 10nmol/LIso后 1μmol/LACh对Fc有间接的抑制作用 ,快速冲洗ACh后亦引起Fc的反跳性增强 ,与Iso组相比增强了 2 7.1%±13.2 % (n =7,P <0 .0 1)。 1μmol/LACh对心室肌细胞基础峰电流无明显影响 (n =8,P >0 .0 5 ) ;而以基础ICa L峰值(931± 16 1pA)作对照 ,在加入 10nmol/LIso后 ,ICa L峰电流增强到 1889± 331pA(n =7,P <0 .0 1) ;再给予 10nmol/LIso +1μmol/LACh快速灌流 2min ,峰电流降低为 15 12± 2 0 2pA(P <0 .0 1) ,用含 10nmol/LIso的细胞外液快速洗脱ACh ,峰电流增强到 2 10 7± 2 0 5pA ,较Iso组反跳性增强了 15 .8%± 4 .0 % (n =7,P <0 .0 1)。结论 :ACh对豚鼠心室肌收缩

Acetylcholine Elicits a Rebound Stimulation of Force Contraction and L-type Ca2+ Current in Guinea-Pig Ventricle.

To observe acetylcholine(ACh) elicits a rebound stimulation of force contraction(Fc) and L type Ca 2+ current in guinea pig ventricle,and study its mechanisms.The direct and indirect (the effects induced by 10 nmol/L isoproterenol)effects of 1 μmol/L ACh on cardiac ventricle Fc was observed by using isolated papillary muscles from guinea pig left ventricles,and observed the effects of 1 μmol/L ACh and 10 nmol/L Iso+1 μmol/L ACh on L type Ca 2+ current in guinea pig ventricular myocytes by using whole cell configuration of the patch clamp techinque.Results:Stimulation of contractility and I Ca L caused by 10 nmol/L Iso were attenuated in the presence of 1 μmol/L ACh,but were transiently enhanced by 27.1%±13.2%( n=7,P <0.01 vs Iso)and 15.8%±4.0%( n=7,P <0.01 vs Iso),respectively,following quickly washout of ACh.I Ca L that no changes were observed in the absence of Iso( n=8,P >0.05).but ACh has direct inhibitory action on the basal force of contraction in papillary muscles from guinea pig left ventricles,and transiently enhanced Fc by 25.5%±10.3%( n=7,P <0.01),by washout of ACh.Conclusion:ACh has direct negative inotropic effect on isolated guinea pig ventricle muscles.Rebound increase of Fc and Iso stimulated I Ca L would happen after termination of an exposure of ventricle myocytes to ACh.