腺苷抗豚鼠室性心律失常的电生理研究(英文)

An electrophysiological study on the anti-ventricular arrhythmic effect of adenosine in the guinea pig

实验用全细胞膜片钳技术在单个豚鼠心室肌细胞上研究了腺苷 (Ado)对正常及异丙肾上腺素 (Iso)致豚鼠心室肌细胞动作电位、迟后除极 (DAD)、L 型钙电流 (ICa.L)和短暂内向电流 (Iti)的作用。结果表明 :(1)Ado在2 0～ 10 0 μmol/L时对豚鼠心室肌细胞动作电位和ICa .L无明显直接作用 ,但却可明显降低Iso所致的动作电位时程(APD)延长和ICa .L峰值增大 ,Iso (10nmol/L)使细胞APD50 从 3 40± 2 1ms延长到 486± 2 8ms (P <0 0 1) ,APD90从 3 61± 17ms延长至 5 0 1± 2 9ms (P <0 0 1) ;ICa .L峰值从 - 6 5 3± 1 4pA/pF增大到 - 18 2 8± 2 4pA/pF (P <0 0 1) ,电流电压曲线明显左移和下移 ;Ado (5 0 μmol/L)使APD50 和APD90 降至 40 3± 19ms和 419± 2 6ms ,但并不影响动作电位其它参数 ,使ICa.L峰值降低至 - 10 2± 1 5pA/pF (P <0 0 1)。 (2 )Iso (3 0nmol/L)可诱发心室肌细胞产生DADs,其发生率为 10 0 % ;Ado (5 0 μmol/L)可完全抑制Iso引发DADs;细胞经 - 40～ +2 0mV、时程 2s的除极电压 ,Iso (3 0nmol/L)诱导出Iti,其发生率为 10 0 % ;Ado (5 0 μmol/L)可明显抑制Iso致Iti的发生 ,其发生率降为 14 3 %。研究结果提示 ,Ado对豚鼠心室肌细胞动作电位和ICa.L无明显直接作用 。

Using whole cell patch clamp technique this study investigated the effects of adenosine (Ado) on action potential, L type calcium current ( I Ca.L ), delayed afterdepolarizations (DADs), and transient inward current ( I ti ) induced by isoproterenol (Iso) in guinea pig isolated single ventricular myocytes. The results showed: (1) Ado alone had no significant direct effects on action potential and I Ca.L in guinea pig ventricular myocytes at 20～100 μmol/L. However, Ado significantly attenuated the prolongation of action potential duration (APD) and the increase of the peak amplitude of I Ca.L induced by Iso. Iso (10 nmol/L) markedly increased APD 50 and APD 90 from 340±21 ms to 486±28 ms and from 361±17 ms to 501±29 ms, respectively ( P <0 01), and increased the amplitude of I Ca.L from -6 53 ±1 4 pA/pF to -18 28 ±2 4 pA/pF ( P <0 01). The peak potential of current potential relationship shifted to the left. Ado (50 μmol/L) abbreviated APD 50 , APD 90 to 403±19 ms and 419±26 ms ( P <0 01), and decreased the peak amplitude of I Ca.L to -10 2 ±1 5 pA/pF ( P <0 01 vs Iso), but did not change resting membrane potential (RMP), action potential amplitude (APA), and overshoot (OS). (2) Iso (30 nmol/L) reproducibly elicited DADs with 100% incidence of DADs under this condition. Ado (50 μmol/L)completely inhibited Iso from inducing DADs. Iso (30 nmol/L) elicited I ti with 2 second depolarizing voltage clamp pulses rising to +20 mV from a holding potential of -40 mV, the incidence of I ti being 100%, and the I ti was suppressed in the presence of Ado (50 μmol/L) with the incidence of I ti decreased to 14 3% ( P <0 05). These data indicate that Ado antagonizes the stimulatory effect of Iso, and that the antiarrhythmic mechanism of Ado preventing Iso induced DADs is due to the inhibition of intracellular Ca 2+ overload through attenuating the prolongation of APD, the enhance of I Ca.L and I ti .