T-type Cav3.3 calcium channels produce spontaneous low-threshold action potentials and intracellular calcium oscillations
T-type Cav3.3 calcium channels produce spontaneous low-threshold action potentials and intracellular calcium oscillations
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DOI：
10.1111/j.1460-9568.2006.04761.x
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Quignard, Jean-Francois
中科院分区：
文献类型：
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作者：
Chevalier, Marc;Lory, Philippe;Quignard, Jean-Francois
T-型钙通道在产生动作电位、爆发放电和细胞内钙信号中的确切作用有待进一步阐明。在这里，我们表明，Ca（v）3.3通道可以触发重复AP，产生自发的膜电位振荡（MPO），并在细胞内Ca 2+浓度（[Ca 2 +]（i））的同时增加时，在NG 108 -15细胞过表达。MPO依赖于Ca（v）3.3通道活性，因为它们是在-55至-70 mV的电位范围内记录的，被镍和米贝拉地尔以及低外部Ca 2+浓度阻断。记录不同持续时间的AP：短AP（sAP）或长AP（pAP），平台电位接近-40 mV。Ca（v）3.3通道的电压依赖性限制了AP的持续时间，并且通过Ca（v）3.3通道的持续钙电流支持平台电位。静息保持电位去极化时，持续电流幅度下降，从而诱导AP形状从pAP到sAP的转换。[Ca ~（2+）]（i）振荡的持续时间也与AP的形状密切相关。Ca（v）3.3窗口电流是振荡触发器，如通过作为增加外部Ca 2+浓度的结果而移动Ca（v）3.3窗口电流电位范围所示，这导致AP阈值的相应移动。总的来说，数据表明Ca（v）3.3窗口电流在触发固有电振荡和[Ca 2 +]（i）振荡中是关键的。Ca（v）3.3通道的功能性表达可通过其窗口电流产生自发的低阈值钙激活电位，表明Ca（v）3.3通道在起搏活动中起主要作用。
The precise contribution of T-type Ca2+ channels in generating action potentials (APs), burst firing and intracellular Ca2+ signals needs further elucidation. Here, we show that Ca(v)3.3 channels can trigger repetitive APs, generating spontaneous membrane potential oscillations (MPOs), and a concomitant increase in the intracellular Ca2+ concentration ([Ca2+](i)) when overexpressed in NG108-15 cells. MPOs were dependent on Ca(v)3.3 channel activity given that they were recorded from a potential range of -55 to -70 mV, blocked by nickel and mibefradil, as well as by low external Ca2+ concentration. APs of distinct duration were recorded: short APs (sAP) or prolonged APs (pAP) with a plateau potential near -40 mV. The voltage-dependent properties of the Ca(v)3.3 channels constrained the AP duration and the plateau potential was supported by sustained calcium current through Ca(v)3.3 channels. The sustained current amplitude decreased when the resting holding potential was depolarized, thereby inducing a switch of AP shape from pAP to sAP. Duration of the [Ca2+](i) oscillations was also closely related to the shape of APs. The Ca(v)3.3 window current was the oscillation trigger as shown by shifting the Ca(v)3.3 window current potential range as a result of increasing the external Ca2+ concentration, which resulted in a corresponding shift of the AP threshold. Overall, the data demonstrate that the Ca(v)3.3 window current is critical in triggering intrinsic electrical and [Ca2+](i) oscillations. The functional expression of Ca(v)3.3 channels can generate spontaneous low-threshold calcium APs through its window current, indicating that Ca(v)3.3 channels can play a primary role in pacemaker activity.