STRETCH-ACTIVATED CHANNELS IN HEART-CELLS - RELEVANCE TO CARDIAC-HYPERTROPHY
STRETCH-ACTIVATED CHANNELS IN HEART-CELLS - RELEVANCE TO CARDIAC-HYPERTROPHY
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DOI：
10.1097/00005344-199117002-00024
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发表时间：
1991-01-01
影响因子：
3
通讯作者：
SACHS, F
中科院分区：
文献类型：
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作者：
BUSTAMANTE, JO;RUKNUDIN, A;SACHS, F
牵张激活通道被认为是心肌肥厚中负荷和蛋白质合成之间的转导机制。 根据这一假设，心脏变形与钠（Na）内流增加有关，这反过来又增加了蛋白质合成。 我们已经测试了是否strech实际上增加钠流入应用膜片钳技术培养的鸡胚心肌细胞和新鲜分离的成年豚鼠心肌细胞。 我们的实验，在切除和细胞附着的补丁，揭示了离子通道的存在，打开，或增加其开放的频率，在应用负压的膜片钳移液器的管腔。 这些拉伸敏感通道允许主要的单价生理阳离子Na和钾（K）通过，并且在小得多的程度上允许主要的二价阳离子钙（Ca）和镁（Mg）通过。 在正常情况下，通道具有高的开放通道噪声，这妨碍了对单通道数据进行常规的、直接的统计分析。 然而，当主要的一价阳离子之一被蔗糖等电位取代时，开放通道噪声显著降低，并允许良好地描绘开放和闭合通道状态，因此，应用标准膜片钳，统计分析技术。 在这些“蔗糖”、“单离子”条件下，如人们所预期的，反转电位接近存在的主要一价阳离子的平衡电位。 当使用高细胞外K溶液来最大限度地降低细胞静息电位时，这些牵张激活电流的逆转电位估计约为-40 mV。 因此，在正常情况下，拉伸应诱导向内的去极化电流，主要由Na离子携带。 该牵张激活电流的电压依赖性将确保在牵张期间，膜去极化不超过牵张激活通道的反转电位。 最后，这些通道不渗透阴离子，并完全阻断100 μ M钆。 我们的实验结果支持这一概念，即增加负荷导致增加钠流入的建议。
Stretch-activated channels have been proposed as the transduction mechanism between load and protein synthesis in cardiac hypertrophy. Under this hypothesis, cardiac deformation is linked to an increased sodium (Na) influx, which, in turn, increases protein synthesis. We have tested whether strech actually increases Na influx by applying patch-clamp techniques to cultured chick embryo cardiac myocytes and to freshly isolated adult guinea pig cardiomyocytes. Our experiments, in excised and cell-attached patches, revealed the existence of ionic channels that opened, or increased their frequency of opening, upon the application of negative pressures to the lumen of the patch-clamp pipettes. These stretch-sensitive channels allowed the passage of the major monovalent physiological cations, Na and potassium (K), and, to a much lesser extent, the major divalent cations calcium (Ca) and magnesium (Mg). Under normal conditions, the channels had a high open channel noise that prevented the customary, straightforward statistical analysis of single channel data. However, when one of the major monovalent cations was iso-osmotically replaced by sucrose, the open channel noise decreased significantly and permitted a good delineation of the open and closed channel states and, therefore, application of standard patch-clamp, statistical analysis techniques. Under these "sucrose," "monoionic" conditions, the reversal potential was, as one should expect, close to the equilibrium potential for the major monovalent cation present. When high extracellular K solution was used to minimize the cell resting potential, the reversal potential for these stretch-activated currents was estimated to be around -40 mV. Therefore, under normal conditions, stretch should induce an inward, depolarizing current, carried mostly by Na ions. The voltage dependence of this stretch-activated current would insure that, during stretch, membrane depolarization does not go beyond the reversal potential of the stretch-activated channel. Finally, these channels were not permeant to anions and were completely blocked by 100-mu-M gadolinium. Our experimental results support the concept that increased load leads to an augmented sodium influx as proposed.