Modulation of cardiac Na+ current by gadolinium, a blocker of stretch-induced arrhythmias
Modulation of cardiac Na+ current by gadolinium, a blocker of stretch-induced arrhythmias
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DOI：
10.1152/ajpheart.2001.280.1.h272
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发表时间：
2001-01-01
影响因子：
4.8
通讯作者：
Baumgarten, CM
中科院分区：
文献类型：
--
作者：
Li, GR;Baumgarten, CM
Gd 3+阻断牵张激活的通道并抑制牵张诱导的心律失常。我们使用全细胞电压钳来检查对Na+通道的影响是否可能有助于Gd 3+的抗心律失常功效。Gd ~（3+）抑制兔心室肌Na ~+电流（I-Na）（IC_（50））= 48 μ M（-35 mV，保持电位-120 mV），在更负的测试电位下阻滞增强。Gd ~（3+）使INa的阈值偏正，最大电导降低。Gd ~（3+）（50 μ M）使I-Na激活和失活的中点移动7.9和5.7 mV，但没有改变两种关系的斜率因子。活化和失活动力学减慢的方式，不能解释仅仅通过改变表面电位。在一定条件下，Gd ~（3+）使I-Na增加。当膜电位保持在-75 mV时，Gd 3+仍然使激活阈值正移，但INa增加到正向-40 mV，导致电流-电压曲线交叉。当可用性最初较低时，由Gd 3+诱导的可用性增加在测试电位为正至-40 mV时占主导地位。结果表明，Gd ~（3+）对心肌Na ~+通道具有复杂的作用。Gd ~（3+）在阈电位附近是一种有效的I-Na阻滞剂，与保持电位无关，Gd ~（3+）对I-Na的抑制可能有助于抑制牵张诱发的心律失常。
Gd3+ blocks stretch-activated channels and suppresses stretch-induced arrhythmias. We used whole cell voltage clamp to examine whether effects on Na+ channels might contribute to the antiarrhythmic efficacy of Gd3+. Gd3+ inhibited Na+ current (I-Na) in rabbit ventricle (IC50 = 48 muM at -35 mV, holding potential -120 mV), and block increased at more negative test potentials. Gd3+ made the threshold for INa more positive and reduced the maximum conductance. Gd3+ (50 muM) shifted the midpoints for activation and inactivation of I-Na 7.9 and 5.7 mV positive but did not alter the slope factor for either relationship. Activation and inactivation kinetics were slowed in a manner that could not be explained solely by altered surface potential. Paradoxically, Gd3+ increased I-Na under certain conditions. With membrane potential held at -75 mV, Gd3+ still shifted threshold for activation positive, but INa increased positive to -40 mV, causing the current-voltage curves to cross over. When availability initially was low, increased availability induced by Gd3+ dominated the response at test potentials positive to -40 mV. The results indicate that Gd3+ has complex effects on cardiac Na+ channels. Independent of holding potential, Gd3+ is a potent I-Na blocker near threshold potential, and inhibition of I-Na by Gd3+ is likely to contribute to suppression of stretch-induced arrhythmias.