Differential modulation of N-type α1B and P/Q-type α1A calcium channels by different G protein β subunit isoforms
Differential modulation of N-type α1B and P/Q-type α1A calcium channels by different G protein β subunit isoforms
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DOI：
10.1111/j.1469-7793.2000.00203.x
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发表时间：
2000-09-01
影响因子：
5.5
通讯作者：
Zamponi, GW
中科院分区：
文献类型：
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作者：
Arnot, MI;Stotz, SC;Zamponi, GW
1.采用瞬时钙磷脂转染人胚胎肾TSA-201细胞系和随后的全细胞膜片钳方法，我们观察了不同G蛋白β亚基通过强去极化电压预脉冲对克隆的N-型和P/Q型钙通道的紧张性调节作用。对于N型和P/Q型通道，抑制的程度取决于共表达的G(Beta)亚型。G(β)亚基对P/Q型通道的绝对和相对抑制幅度均不同于N型通道。对于每一种钙通道亚型，通过改变前脉冲和测试脉冲之间的持续时间或前脉冲的长度，对每个G(β)亚基的前脉冲介导的抑制恢复和前脉冲后的再抑制的动力学进行了研究。对于每个通道亚型，我们观察到关于再抑制和从抑制中恢复的速率的G(β)亚单位的不同排序。平均而言，P/Q型通道表现出比N型通道更快的恢复速度。不同的G(β)亚型介导了不同程度的激活动力学减慢。不同G(β)亚型对P/Q和N型通道的不同调制可能为微调进入突触前神经末梢的钙量提供了一种机制。
1. Using transient calcium phosphate transfection into the human embryonic kidney tsa-201 cell line and subsequent whole-cell patch-clamp protocols, we examined the tonic modulation of cloned N- and P/Q-type calcium channels by fire different G protein beta subunits via strong depolarizing voltage prepulses.2. For N- and P/Q-type channels, the magnitude of inhibition was dependent on the G(beta) subtype co-expressed.3. Both the absolute and relative magnitudes of G(beta) subunit-induced inhibition of P/Q-type channels differed from those observed with the N-type channel.4. For each calcium channel subtype, kinetics of both the prepulse-mediated recovery from inhibition and the re-inhibition following the prepulse were examined for each of the G(beta) subunits by varying either the duration between the pre- and the test pulse or the length of the prepulse5. For each channel subtype, we observed a differential G(beta) subunit rank order with regard to the rates of re-inhibition and recovery from inhibition.6. On average, P/Q-type channels exhibited more rapid rates of recovery from inhibition than those observed with N-type channels.7. Different G(beta) subtypes mediated different degrees of slowing of activation kinetics.8. The differential modulation of P/Q- and N-type channels by various G(beta) subtypes may provide a mechanism for fine tuning the amount of calcium entering the presynaptic nerve termini.