Liu Gang, Zheng Ming-qi, Wang Wei, Wang Xiao-yu, Ma Fang-fang, Yu Hong-fang, Li Xue-yong
Department of Cardiology,The First Hospital of Hebei Medical University, Shijiazhuang 050031, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2011 Dec 18;43(6):804-8.
To study the effect of lysophosphatidylcholine (LPC) on T-type calcium channel currents (I(Ca.T)) in cardiomyocytes, and identify the mechanism by which LPC accumulation in intracellular and/or interstitial space may uptake tachycardia and various arrhythmias during cardiac ischemia.
Neonatal rat cardiomyocytes from 1 to 3-day-old Wistar rats and hypertrophied ventricular myocytes from Wistar rats were prepared. Human cardiac T-type calcium channel α1 subunits, Ca(V3.1) and Ca(V3.2), were stably expressed in HEK293 cells. In this study, cardiomyocytes and heterologous expression of human Ca(V3.1) and Ca(V3.2) components were measureed by whole-cell patch clamp to study the up-regulation of I(Ca.T) by LPC.
LPC markedly accelerated the spontaneous beating rates of neonatal rat cardiomyocytes from (42±8) beats/min in control to (64 ±8) beats/min after LPC application for 5 min at the physiological Ca(2+) concentration (pCa=7.2). In neonatal cardiomyocytes, I(Ca.T) was significantly increased by 10 μmol/L LPC by 21.5% when Ca(2+) was high (pCa=7). Intracellular Ca(2+)-dependent augmentation of I(Ca.T) by LPC was confirmed not only in neonatal cardiomyocytes but also in adult ventricular myocytes from the hypertrophied hearts. In this experiment, I(Ca.T) was significantly increased by 10 μmol/L LPC by 23.5% when Ca(2+) was high (pCa=7), although it was unchanged when Ca(2+) was low (pCa=11), control: (3.8±0.2) pA/pF, n=16; LPC: (3.7±0.4) pA/pF, n=10. LPC exerted no effect on the Ca(V3.1) T-type Ca(2+) channel current (I(Ca(V)3.1)) regardless of the Ca(2+) concentration at a pCa of 7 or at a pCa of 11. In contrast, LPC up-regulated the Ca(V3.2) T-type Ca(2+) channel current (I(Ca(V)3.2)), which was much larger at a pCa of 7 [LPC=10 μmol/L: (68.8±2.1) pA/pF, n=10; LPC=50 μmol/L: (78.4±4.8) pA/pF, n=9)] than that at a pCa of 11 [(38.5±2.1) pA/pF, n=11].
The present study indicates that LPC up-regulates the cardiac I(Ca.T) in physiological or higher Ca(2+) concentration, which may accelerate the pathophysiological cardiac automaticity and trigger tachyarrhythmias as novel ischemia-related mechanism.
研究溶血磷脂酰胆碱（LPC）对心肌细胞T型钙通道电流（I(Ca.T)）的影响，并确定细胞内和/或细胞间质中LPC蓄积可能在心脏缺血期间引发心动过速和各种心律失常的机制。
制备1至3日龄Wistar大鼠的新生大鼠心肌细胞以及Wistar大鼠的肥厚心室肌细胞。人心脏T型钙通道α1亚基Ca(V3.1)和Ca(V3.2)在HEK293细胞中稳定表达。在本研究中，通过全细胞膜片钳测量心肌细胞以及人Ca(V3.1)和Ca(V3.2)成分的异源表达，以研究LPC对I(Ca.T)的上调作用。
在生理[Ca(2+)]i浓度（pCa = 7.2）下，LPC作用5分钟后，新生大鼠心肌细胞的自发搏动率从对照时的（42±8）次/分钟显著加快至（64±8）次/分钟。在新生心肌细胞中，当[Ca(2+)]i较高（pCa = 7）时，10 μmol/L LPC可使I(Ca.T)显著增加21.5%。LPC对I(Ca.T)的细胞内Ca(2+)依赖性增强不仅在新生心肌细胞中得到证实，在肥厚心脏的成年心室肌细胞中也得到证实。在本实验中，当[Ca(2+)]i较高（pCa = 7）时，10 μmol/L LPC可使I(Ca.T)显著增加23.5%，而当[Ca(2+)]i较低（pCa = 11）时I(Ca.T)无变化，对照：（3.8±0.2）pA/pF，n = 16；LPC：（3.7±0.4）pA/pF，n = 10。无论pCa为7还是pCa为11时的[Ca(2+)]i浓度如何，LPC对Ca(V3.1) T型钙通道电流（I(Ca(V)3.1)）均无影响。相反，LPC上调了Ca(V3.2) T型钙通道电流（I(Ca(V)3.2)），在pCa为7时[LPC = 10 μmol/L：（68.8±2.1）pA/pF，n = 10；LPC = 50 μmol/L：（78.4±4.8）pA/pF，n = 9]比在pCa为11时[（38.5±2.1）pA/pF，n = 11]大得多。
本研究表明，在生理或更高的[Ca(2+)]i浓度下，LPC上调心脏I(Ca.T)，这可能加速病理生理性心脏自律性并引发快速性心律失常，是一种新的缺血相关机制。
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