血小板活化因子对豚鼠心室肌细胞动作电位和钾通道的影响(英文)

Effects of platelet activating factor on action potentials and potassium channels in guinea-pig ventricular myocytes

应用全细胞膜片钳技术研究了皿小板活化因子(platelet activating factor,PAF)对豚鼠心室肌细胞动作电位和钾电流的影响。结果发现,当电极内液ATP浓度为5mmol/L(模拟正常条件)时,1μmol/L PAF使APD_(90)由对照的225.8±23.3ms延长至352.8±29.8ms(n=5,P<0.05);使I_K尾电流在指令电压+30mV由对照的173.5±16.7pA降至152.1±11.5pA(P<0.05,n=4);使I_(K1)在指令电压为-120mV时由对照组的-6.1±1.3nA降至-5.6±1.1nA(P<0.05,n=5);但PAF在生理膜电位范围(-90mV～+20mV)对I_(K1)没有影啊。当电极内液ATP浓度为0mmol/L时,I_(K-ATP)开放(模拟缺血条件),1μmol/L PAF却显著缩短APD_(90),由对照的153±24.6ms缩短至88.2±19.4ms(n=5,P<0.01)。而用1μmol/L格列本脲(I_(K-ATP)的特异阻断剂)预处理后,恢复了PAF可显著延长动作电位时程的作用。结果提示,PAF可能扩大缺血心肌和正常心肌细胞动作电位时程的不均一性。

This study was designed to investigate the effects of platelet activating factor (PAF) on the action potential and potassium currents in guinea-pig ventricular myocytes. Whole cell patch clamp techniques were used. With 5 mmol/L ATP in the pipette electrode (mimic normal condition), 1 μmol/L PAF increased APD_(90), from 225.8±23.3 to 352.8±29.8 ms (n=5, P<0.05), decreased I_(K1) and I_K tail currents from -6. 1±1.3 to -5.6±1.1 nA (n=5, P<0.05) at -120 mV and from 173.5±6.7 to 152.1±11.5 pA (P<0.05, n=4) at+30mV, respectively. But PAF had no effect on I_(K1) at potentials within the normal range of membrane potentials (between -90 mV and+20mV). In the contrary, without ATP in the pipette electrode by which I_(K·ATP) was activated (mimic ischemic condition), 1 μmol/L PAF shortened APD_(90) from 153±24.6 to 88.2±19.4 ms (n=5, P<0.01). Incubation of myocytes with 1 μmol/L glibenclamide, a blocker of I_(K·ATP) could restore prolongation of APD induced by PAF. In conclusion, in guinea-pig ventricular myocytes, with 5 mmol/L ATP in the pipette PAF could prolong APD partly due to the inhibition of I_K; while with 0 mmol/L ATP in the pipette, PAF could induce an activation of I_(K·ATP), hence a decrease in APD. It is suggested that PAF may amplify the heterogeneity between ischemic and normal cardiac myocytes during ischemia/reperfusion, which may play a vital role in the pathogenesis of the arrhythmias induced by ischemia/reperfusion.