Nuss H B, Houser S R
Department of Physiology, Temple University School of Medicine, Philadelphia, Pa 19140.
Circ Res. 1993 Oct;73(4):777-82. doi: 10.1161/01.res.73.4.777.
Macroscopic T-type Ca2+ currents, which are often observed in fetal and neonatal cardiac muscle cells, were not found in normal (0 of 17) adult feline ventricular myocytes. However, they were present in most (15 of 21) myocytes isolated from adult feline left ventricles with long-standing pressure-overload-induced hypertrophy. This is the first study to provide evidence in a large mammal, such as the cat, that T-type Ca2+ channels may be reexpressed in adults in association with hypertrophy resulting from slow progressive pressure overload. Importantly, this expression was stable for the duration of the hypertrophy process and was not associated with abrupt pressure overload. T-type Ca2+ currents were separated from L-type Ca2+ currents by exploiting the differences in their voltage dependence of steady-state inactivation. Depolarizations from -80 mV revealed a rapidly activating inward current that peaked in magnitude at -30 mV (-1.8 +/- 0.9 [mean +/- SD] pA/pF) and fully inactivated within 100 milliseconds in 15 of 21 hypertrophied myocytes studied. Further depolarizations activated progressively less T-type Ca2+ current, so that at +10 mV the L-type Ca2+ current predominated. In the hypertrophied myocytes that demonstrated both T-type and L-type Ca2+ currents, two distinct peaks occurred in their current-voltage relations. T-type Ca2+ currents were not evident in any of the 17 normal adult feline left ventricular myocytes studied. The purpose of T-type Ca2+ currents in hypertrophy is unclear. However, their presence may make hypertrophied myocardium more prone to spontaneous action potentials and increase the likelihood for arrhythmias in partially depolarized hypertrophied myocardium.
宏观T型钙电流常见于胎儿和新生儿心肌细胞中,但在正常成年猫心室肌细胞中未检测到(17个样本中为0个)。然而,在大多数(21个样本中有15个)从患有长期压力超负荷诱导性肥大的成年猫左心室分离出的心肌细胞中,这种电流是存在的。这是首次在大型哺乳动物(如猫)中提供证据表明,T型钙通道可能在成年动物中与缓慢进行性压力超负荷导致的肥大相关而重新表达。重要的是,这种表达在肥大过程中持续稳定,并且与突然的压力超负荷无关。通过利用T型钙电流和L型钙电流在稳态失活电压依赖性上的差异,将它们区分开来。从-80 mV去极化显示出一个快速激活的内向电流,在-30 mV时达到峰值(-1.8±0.9[平均值±标准差]pA/pF),在研究的21个肥大心肌细胞中的15个中,该电流在100毫秒内完全失活。进一步去极化逐渐激活较少的T型钙电流,因此在+10 mV时,L型钙电流占主导。在同时表现出T型和L型钙电流的肥大心肌细胞中,其电流-电压关系出现两个不同的峰值。在所研究的17个正常成年猫左心室心肌细胞中,均未发现T型钙电流。肥大过程中T型钙电流的作用尚不清楚。然而,它们的存在可能使肥大心肌更容易产生自发动作电位,并增加部分去极化的肥大心肌发生心律失常的可能性。