Distinct kinetics of cloned T-type Ca2+ channels lead to differential Ca2+ entry and frequency-dependence during mock action potentials
Distinct kinetics of cloned T-type Ca2+ channels lead to differential Ca2+ entry and frequency-dependence during mock action potentials
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DOI：
10.1046/j.1460-9568.1999.00841.x
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发表时间：
1999-12-01
影响因子：
3.4
通讯作者：
Lambert, RC
中科院分区：
文献类型：
--
作者：
Kozlov, AS;McKenna, F;Lambert, RC
静息电位周围的电压依赖性活动在神经元生理学中是决定性的，并且参与放电模式的定义。低电压激活的T型钙通道直接影响膜电位，并控制许多次级钙依赖性通透性。我们研究了克隆的T型通道（α 1G，H，I）响应模拟动作电位携带Ca 2+电流的能力。尖峰持续时间和电流幅度之间的关系是特定的每个T型通道，反映其各自的动力学特性。通常，电荷转移随着尖峰加宽而增加，但根据通道类型，总Ca 2+进入在不同的尖峰持续时间饱和：α 1G为4 ms; α 1H为7 ms; α 1 I通道> 10 ms。在爆发期间，根据α 1通道类型，电流被抑制和/或瞬时增强，在较高频率下具有较大影响。抑制可以通过电压依赖性向失活状态的转变和/或通过中间闭合状态的通道失活来诱导。的增强解释通道激活动力学的加速。相对快速的失活和缓慢的恢复限制了α 1G和α 1H通道对高频刺激（> 20 Hz）的反应能力。相反，α 1 I亚基的缓慢失活允许这些通道继续参与高频爆发（100 Hz）。因此，α 1G、H和I通道的生物物理特性将显著调节神经元活动对Ca 2+信号传导的影响。
Voltage-dependent activity around the resting potential is determinant in neuronal physiology and participates in the definition of the firing pattern. Low-voltage-activated T-type Ca2+ channels directly affect the membrane potential and control a number of secondary Ca2+-dependent permeabilities. We have studied the ability of the cloned T-type channels (alpha 1G,H,I) to carry Ca2+ currents in response to mock action potentials. The relationship between the spike duration and the current amplitude is specific for each of the T-type channels, reflecting their individual kinetic properties. Typically the charge transfer increases with spike broadening, but the total Ca2+ entry saturates at different spike durations according to the channel type: 4 ms for alpha 1G; 7 ms for alpha 1H; and > 10 ms for alpha 1I channels. During bursts, currents are inhibited and/or transiently potentiated according to the alpha 1 channel type, with larger effects at higher frequency. The inhibition may be induced by voltage-independent transitions toward inactivated states and/or channel inactivation through intermediate closed states. The potentiation is explained by an acceleration in the channel activation kinetics. Relatively fast inactivation and slow recovery limit the ability of alpha 1G and alpha 1H channels to respond to high frequency stimulation (> 20 Hz). In contrast, the slow inactivation of alpha 1I subunits allows these channels to continue participating in high frequency bursts (100 Hz). The biophysical properties of alpha 1G, H and I channels will therefore dramatically modulate the effect of neuronal activities on Ca2+ signalling.