The relationship between changes in intracellular ion concentrations and the antiarrhythmic effects of stilbene derivatives

采用离子选择微电极技术，通过测定细胞内pH(Phi)和细胞内氯离子(Ac&lt；@D1i@&gt；D1l)，探讨CI&lt；@d1-@&gt；d1-hco&lt；@D3-(/)3@&gt；D3交换器在缺血诱导的豚鼠心肌细胞内酸中毒中的作用。以二苯乙烯类化合物SITS和DIDS为探针，阻断CI&lt；@d1-@&gt；d1-hco&lt；@D3-(/)3@&gt；D3交换器，观察其对模拟缺血心肌动作电位(APs)、Phi和Ac&lt；@D1i@&gt；D1l的影响。停流灌流液造成模拟缺血，用矿物油覆盖制剂。缺血引起最大上搏率和静息膜电位进行性下降，动作电位时程缩短，导致AP停止。SITS(0.5 mM)和DDS(0.1 mM)可延缓AP缺血恶化的发生，延长AP的停搏时间。缺血诱导明显的细胞内酸性…更多的SIS(对照的Phi：7.023()Sy.+-.[]0.083；缺血15min的phi：6.64sy.+-。[0.012，n=6]，SITE或DIDS可抑制缺血时细胞内酸中毒的发生。SITS组和DIDS组在缺血后10min和15min的PHi变化与对照组比较差异有统计学意义(p&lt；0.05&gt；在无外源性CI&lt；@d1-@&gt；d1的条件下，缺血时AP停止的时间明显延迟，酸化受到抑制。此外，缺血诱导的Ac&lt；@D1i@&gt；D1l(对照组：18.74(]sy.+-)显著增加。[]9.28 mm；缺血值：55.3(Sy.+-)。[)6.11 mM]，这种增加被外部CI&lt；@d1-@&gt；d1-或二苯乙烯衍生物抑制。本研究结果表明，CI&lt；@d1-@&gt；d1-hco&lt；@D3-(/)3@&gt；D3交换器的激活参与了缺血时细胞内酸中毒的发生，二苯乙烯类衍生物阻断cI&lt；@d1-@&gt；d1-hco&lt；@D3-(/)3@&gt；d3-(/)3@&gt；D3交换可减轻缺血诱导的细胞内酸中毒，从而对缺血诱导的心律失常有良好的治疗作用。较少

We investigated the possible role of CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger on ischemia-induced intracellular acidosis in isolated guinea pig ventricular muscle by measuring intracellular pH (pHi) and intracellular chloride (aC<@D1i@>D1l) with ion-selective microelectrode techniques. Stilbene derivatives, SITS and DIDS,were used as probes to block the CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger and their effects on action potentials (APs) , pHi and aC<@D1i@>D1l in ventricular muscles subjected to simulated ischemia were examined. Simulated ischmia was produced by stopping flow of superfusing solution and preparations were covered with mineral oil. Ischemia induced a progressive decrease in the maximum upstroke rate and resting membrane potentials, and shortened action potential duration, resulting in cessation of APs. SITS (0.5mM) and DIDS (0.1mM) delayd the onset of ischemia-induced deterioration of APs and prolonged the time to cessation of APs. Ischemia induced marked intracellular acido … More sis (pHi of control : 7.023(]SY.+-。[)0.083 ; pHi at 15 min after ischemia : 6.64(]SY.+-。[)0.012, n=6), and SITS or DIDS suppressed the development of intracellular acidosis during ischemia. There were significant differences in pHi change of SITS or DIDS-treated group at 10 and 15 min after ischemia compared with that of control group (p<0.05> . Under an external CI<@D1-@>D1-free condition, the time to cessation of APs during ischemia significantly delayd, and the acidification was suppressed. Furthermore, ischemia induced a great increase in aC<@D1i@>D1l (control : 18.74(]SY.+-。[)9.28mM ; ischemia : 55.3(]SY.+-。[)6.11mM] and this increase was suppressed by the external CI<@D1-@>D1-free or by stilbene derivatives. Present results indicate that activation of CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger is involved in the development of intracellular acidosis occurring during ischemia and that manipulation of pHi and aC<@D1i@>D1l by blocking CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchange by stilbene derivatives can attenuate ischemia-induced intracellular acidosis, thereby having beneficial effects on ischemia-induced arrhythmias. Less