Cav 1 . 4 1 Subunits Can Form Slowly Inactivating Dihydropyridine-Sensitive L-Type Ca 2 Channels Lacking Ca 2-Dependent Inactivation
Cav 1 . 4 1 Subunits Can Form Slowly Inactivating Dihydropyridine-Sensitive L-Type Ca 2 Channels Lacking Ca 2-Dependent Inactivation
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发表时间：
2003
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通讯作者：
A. Koschak;D. Reimer;D. Walter;J. Hoda;Thomas Heinzle;M. Grabner;J. Striessnig
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作者：
A. Koschak;D. Reimer;D. Walter;J. Hoda;Thomas Heinzle;M. Grabner;J. Striessnig
神经元L型钙通道Cav1.2 1和Cav1.3 1在功能上是不同的。Cav1.31在较低电压下激活，比Cav1.21失活更慢，使其适合于支持持续的L型Ca 2内向电流（伊卡，L）并用于起搏功能。我们比较了生物物理和药理学特性的人视网膜Cav1.4 1使用全细胞膜片钳技术后，异源表达在tsA-201细胞与其他L-1型亚基。Cav1.4 1介导的内向Ba 2电流（IBa）需要2 1和3或2a亚基的共表达，并且在比Cav1.3 1更低比例的转染细胞中检测到。IBa在比Cav1.2 1更负的电压（5%激活阈值; 39 mV; 15 mM Ba 2）下激活，并且比Cav1.3 1稍微更正。IBa的电压依赖性失活慢于Cav1.2 1和Cav1.3 1（5秒后50%失活; 2 1 3共表达）。失活没有增加与钙2作为电荷载体，表明缺乏钙2依赖性失活。Cav1.4 1在强去极化脉冲作用下表现出电压依赖性、G蛋白非依赖性的易化作用。二氢吡啶（DHP）-拮抗剂伊拉地平阻断Cav1.4 - 1的敏感性比Cav1.2 - 1低15倍，并以电压依赖性方式。尽管在位置1414（重复IVS 6）处的L型通道特异性酪氨酸残基被苯丙氨酸取代，但发现DHP BayK 8644的强刺激。Cav1.4121通道复合物可形成具有中等DHP拮抗剂敏感性的LTCC，缺乏Ca 2依赖性失活。它们的生物物理特性应使它们能够在负电位下促进持续的伊卡，L，例如感觉细胞中的紧张性神经递质释放和尖峰神经元中的平台电位所需的。
The neuronal L-type calcium channels (LTCCs) Cav1.2 1 and Cav1.3 1 are functionally distinct. Cav1.3 1 activates at lower voltages and inactivates more slowly than Cav1.2 1, making it suitable to support sustained L-type Ca 2 inward currents (ICa,L ) and serve in pacemaker functions. We compared the biophysical and pharmacological properties of human retinal Cav1.4 1 using the whole-cell patchclamp technique after heterologous expression in tsA-201 cells with other L-type 1 subunits. Cav1.4 1-mediated inward Ba 2 currents (IBa ) required the coexpression of 2 1 and 3 or 2a subunits and were detected in a lower proportion of transfected cells than Cav1.3 1. IBa activated at more negative voltages (5% activation threshold; 39mV; 15 mM Ba 2 ) than Cav1.2 1 and slightly more positive than Cav1.3 1. Voltage-dependent inactivation of IBa was slower than for Cav1.2 1 and Cav1.3 1 ( 50% inactivation after 5 sec; 2 1 3 coexpression). Inactivation was not increased with Ca 2 as the charge carrier, indicating the absence of Ca 2 -dependent inactivation. Cav1.4 1 exhibited voltage-dependent, G-protein-independent facilitation by strong depolarizing pulses. The dihydropyridine (DHP)-antagonist isradipine blocked Cav1.4 1 with 15-fold lower sensitivity than Cav1.2 1 and in a voltage-dependent manner. Strong stimulation by the DHP BayK 8644 was found despite the substitution of an otherwise L-type channel-specific tyrosine residue in position 1414 (repeat IVS6) by a phenylalanine. Cav1.4 1 2 1 channel complexes can form LTCCs with intermediate DHP antagonist sensitivity lacking Ca 2 -dependent inactivation. Their biophysical properties should enable them to contribute to sustained ICa,L at negative potentials, such as required for tonic neurotransmitter release in sensory cells and plateau potentials in spiking neurons.