Shander G S, Undrovinas A I, Makielski J C
Department of Medicine, University of Chicago, USA.
J Mol Cell Cardiol. 1996 Apr;28(4):743-53. doi: 10.1006/jmcc.1996.0069.
Lysophosphatidylcholine (LPC), an ischemic metabolite implicated in arrhythmogenesis, has been shown to modulate aspects of Na+ channel gating, but its effects on steady-state availability (h infinity), recovery from inactivation, and the timing of onset and possible reversibility, have not been characterized. We studied Na current (INa) by the whole-cell patch clamp technique on isolated rat ventricular myocytes at 22 degrees C with reduced Na+ (45 mM out, 5 mM in) from a holding potential of -150 mV. Changes in the electrophysiological parameters were measured after LPC 10 microM was added to the bath and compared to time controls (TC) taken from the time of seal formation. LPC decreased peak current for a test potential to -30 mV by about 20%. The peak current voltage relationship shifted in a positive direction by about 5 mV after LPC as compared to a small 2 mV negative shift in TC cells. LPC shifted the steady-state availability curve in the hyperpolarizing direction by about 6 mV. LPC perfusion caused a slowing of the decay of INa, and also a slowing of recovery from inactivation. Onset of the effects occurred within 6 min after adding LPC to the bath and were statistically significant with respect to TC cells between 12 and 16 min. In three cells, some of the effects on INa were either arrested or partially reversed by washout and cell survival was less than 20 min if LPC was not removed from the bath. These LPC induced changes in INa would tend to slow conduction and increase refractoriness, effects also seen in acutely ischemic myocardium. We therefore conclude that LPC action on INa may potentiate the arrhythmogenic substrate and that the onset of these changes are sufficiently rapid to play a role in the electrical instability of acute ischemia.
溶血磷脂酰胆碱（LPC）是一种与心律失常发生有关的缺血代谢产物，已被证明可调节钠通道门控的某些方面，但其对稳态可用性（h∞）、失活恢复以及起效时间和可能的可逆性的影响尚未得到明确。我们在22℃下，采用全细胞膜片钳技术，对分离的大鼠心室肌细胞进行研究，细胞外液中钠离子浓度降低（细胞外45 mM，细胞内5 mM），钳制电位为 -150 mV。在浴液中加入10 μM LPC后，测量电生理参数的变化，并与从形成封接时开始的时间对照（TC）进行比较。LPC使测试电位为 -30 mV时的峰值电流降低约20%。与TC细胞中2 mV的小负向偏移相比，LPC作用后峰值电流 - 电压关系正向偏移约5 mV。LPC使稳态可用性曲线向超极化方向偏移约6 mV。LPC灌流导致钠电流衰减减慢，失活恢复也减慢。加入LPC到浴液后6分钟内开始出现效应，在12至16分钟时与TC细胞相比具有统计学意义。在三个细胞中，对钠电流的一些效应通过洗脱被阻止或部分逆转，如果不将LPC从浴液中去除，细胞存活时间小于20分钟。这些LPC诱导的钠电流变化倾向于减慢传导并增加不应期，在急性缺血心肌中也可见到这些效应。因此，我们得出结论，LPC对钠电流的作用可能增强心律失常的底物，并且这些变化的起效足够迅速，可在急性缺血的电不稳定中发挥作用。
