Undrovinas A I, Burnashev N A, Fledervish I A, Dzheniuari K, Iuriavichius I, Ridl Zh, Zablotskaĭte D, Siuĭ Ch, Rozenshtraukh L V
Kardiologiia. 1990 Sep;30(9):69-73.
Changes in balance of transmembrane ionic currents were achieved in two ways: 1) modifying Na current with lysophosphatidylcholine (LPC), a toxic metabolite of ischemia; 2) modifying Ca current with BAY K 8644, an agonist of Ca channels. Elementary current through Na channel were recorded in an inside-out mode using patch clamp techniques. The effects of BAY K 8644 were studied on the transmembrane potential of guinea pig papillary muscle (PM) and sheep Purkinje fibers (PF). Application of LPC (9-25 microns) from the inner side of the membrane caused a peak reduction of averaged Na current and prolonged the time of inactivation. Analysis of single channel behavior revealed that LPC induced long-lasting bursts of openings, resulting in a noninactivated fraction of Na current. The duration of the action potential (AP) of PM increased slightly (20%), while PF AP duration increased progressively with time even at a low BAY K 8644 dose (0.5 microM). Early after-depolarization (EAD) occurred at min 5. After 10-minute drug use, PF became inexcitable at high plateau levels. TTX and ethmozine (1 microM) restored AP. Thus, changes in balance of ion c currents by modifying Na and/or Ca channels may culminate in the occurrence of an additional steady-state potential at plateau levels. The latter may result EAD and re-entry around functionally inexcitable PF. The similarity of mechanisms of arrhythmias induced by ischemia using the presented model is discussed.
1）用溶血磷脂酰胆碱（LPC，一种缺血的毒性代谢产物）改变钠电流；2）用BAY K 8644（一种钙通道激动剂）改变钙电流。使用膜片钳技术以膜内面向外模式记录通过钠通道的基本电流。研究了BAY K 8644对豚鼠乳头肌（PM）和绵羊浦肯野纤维（PF）跨膜电位的影响。从膜内侧施加LPC（9 - 25微米）导致平均钠电流峰值降低，并延长失活时间。单通道行为分析表明，LPC诱导长时间的开放爆发，导致钠电流的非失活部分。PM动作电位（AP）的持续时间略有增加（20%），而即使在低剂量BAY K 8644（0.5微摩尔）下，PF的AP持续时间也随时间逐渐增加。在第5分钟出现早期后去极化（EAD）。用药10分钟后，PF在高平台水平变得不可兴奋。TTX和乙吗噻嗪（1微摩尔）可恢复AP。因此，通过改变钠通道和/或钙通道来改变离子电流平衡可能最终导致在平台水平出现额外的稳态电位。后者可能导致EAD以及围绕功能上不可兴奋的PF发生折返。本文讨论了使用该模型缺血诱导的心律失常机制的相似性。
