ABSTRACT

Low voltage activated (I_Ca-LVA) calcium currents including Cav1.3 and T-type calcium current (I_Ca-T) have not been reported in adult human left ventricular myocytes (HLVMs). We tried to examine their existence and possible correlation with etiology and patient characteristics in a big number of human LVMs isolated from explanted terminally failing (F) hearts, failing hearts with left ventricular assist device (F-LVAD) and nonfailing (NF) human hearts. LVA (I_Ca-LVA) was determined by subtracting L-type Ca²⁺ current (I_Ca-L) recorded with the holding potential of −50 mV from total Ca²⁺ current recorded with the holding potential of −90 mV or −70 mV. I_{Ca- LVA} was further tested with its sensitivity to 100 µM CdCl₂ and tetrodotoxin. Three HLVMs (3 of 137 FHLVMs) from 2 (N = 30 hearts) failing human hearts, of which one was idiopathic and the other was due to primary pulmonary hypertension, were found with I_Ca-LVA. I_Ca-LVA in one FHLVM was not sensitive to 100 µM CdCl₂ while I_Ca-LVA in another two FHLVMs was not sensitive to tetrodotoxin. It peaked at the voltage of −40~-20 mV and had a time-dependent decay faster than I_Ca-L but slower than sodium current (I_Na). I_Ca-LVA was not found in any HLVMs from NF (75 HLVMs from 17 hearts) or F-LVAD hearts (82 HLVMs from 18 hearts) but a statistically significant correlation could not be established. In conclusion, I_Ca-LVA was detected in some HLVMs of a small portion of human hearts that happened to be nonischemic failing hearts.

摘要

成人左心室肌细胞 (HLVM) 中尚未报道低电压激活 (I _Ca-LVA ) 钙电流，包括 Cav1.3 和 T 型钙电流 (I _{Ca-T )。}我们试图在从移植的终末衰竭 (F) 心脏、左心室辅助装置衰竭心脏 (F-LVAD) 和非衰竭 (NF) 人类心脏中分离出的大量人类 LVM 中检验它们的存在以及与病因学和患者特征之间可能的相关性。 。LVA(I _{Ca-LVA )是通过从以-90 mV的保持电位记录的总Ca} ²⁺电流中减去以-50 mV的保持电位记录的L型Ca 2+ 电流(I Ca-L )来确定^的，_或- 70毫伏。I_钙-LVA进一步测试了其对 100 µM CdCl ₂和河豚毒素的敏感性。_{使用 I Ca-LVA}发现了来自 2 个（N = 30 颗心脏）衰竭人类心脏的 3 个 HLVM（137 个 FHLVM 中的 3 个），其中一个是特发性的，另一个是由于原发性肺动脉高压引起的。一个 FHLVM 中的I _{Ca-LVA对 100 µM CdCl 2}不敏感，而另外两个 FHLVM 中的 I _Ca-LVA对河豚毒素不敏感。它在-40~-20 mV 的电压处达到峰值，并且随时间的衰减比 I _Ca-L快，但比钠电流 (I _Na ) 慢。左心室_钙在来自 NF（来自 17 个心脏的 75 个 HLVM）或 F-LVAD 心脏（来自 18 个心脏的 82 个 HLVM）的任何 HLVM 中没有发现，但无法建立统计学上显着的相关性。总之，在一小部分人类心脏（恰好是非缺血性衰竭心脏）的一些 HLVM 中检测到I _{Ca-LVA 。}