Liu Q Y, Rosenberg R L
Department of Pharmacology, University of North Carolina at Chapel Hill 27599-7365, USA.
Biochem Biophys Res Commun. 1996 Nov 12;228(2):252-8. doi: 10.1006/bbrc.1996.1649.
We have studied the effect of a palmitoyl-L-carnitine (L-PC) on single cardiac L-type Ca channels incorporated from porcine ventricular sarcolemma into planar lipid bilayers where we could control the concentration, intracellular and/or extracellular location, and duration of L-PC treatment. We found that 1.0 microM L-PC in either the intracellular or extracellular chamber caused an approximately 8 fold increase in channel open probability when measured within the first minute after L-PC addition. Higher concentrations of L-PC did not increase open probability to the same extent as 1.0 microM. In addition, we found that L-PC had biphasic effects on the open probability of L-type Ca channels, causing an increase in activity immediately after the addition of L-PC, but leading to a decrease in open probability after a few minutes. Higher concentrations of L-PC (10 microM) also caused a decrease in single-channel conductance from 26 to 21 pS (measured in 100 mM external Ba2+). The effects of L-PC were similar on both sides of the channels, suggesting that alterations in the physical properties of the membrane surrounding the channels may be responsible for the effects of L-PC. These changes in Ca channel activity may participate in the generation of abnormal electrical activity and arrhythmogenesis during ischemia.
我们研究了棕榈酰-L-肉碱（L-PC）对从猪心室肌膜整合到平面脂质双分子层中的单个心脏L型钙通道的影响，在此我们能够控制L-PC处理的浓度、细胞内和/或细胞外位置以及持续时间。我们发现，在细胞内或细胞外腔室中加入1.0 microM的L-PC，在加入L-PC后的第一分钟内测量时，通道开放概率增加了约8倍。更高浓度的L-PC并没有像1.0 microM那样使开放概率增加到相同程度。此外，我们发现L-PC对L型钙通道的开放概率有双相作用，在加入L-PC后立即导致活性增加，但几分钟后导致开放概率降低。更高浓度的L-PC（10 microM）也使单通道电导从26 pS降至21 pS（在100 mM外部Ba2+中测量）。L-PC在通道两侧的作用相似，这表明通道周围膜的物理性质改变可能是L-PC作用的原因。钙通道活性的这些变化可能参与缺血期间异常电活动的产生和心律失常的发生。
