腺苷抗豚鼠室性心律失常的电生理研究

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 ,但却可显著降低Is

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

Using whole-cell patch clamp technique this study investigated the effects of adenosine (Ado) on action potential, L-type calcium current (ICa.L), delayed afterdepolarizations (DADs), and transient inward current (Iti) 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 ICa.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 ICa.L induced by Iso. Iso (10 nmol/L) markedly increased APD50 and APD90 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 ICa.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 APD50, APD90 to 403±19 ms and 419±26 ms (P<0.01), and decreased the peak amplitude of ICa.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 Iti with 2-second depolarizing voltage-clamp pulses rising to +20 mV from a holding potential of -40 mV, the incidence of Iti being 100%, and the Iti was suppressed in the presence of Ado (50 μmol/L) with the incidence of Iti 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 Ca2+ overload through attenuating the prolongation of APD, the enhance of ICa.L and Iti.