Both N- and C-lobes of calmodulin are required for Ca2+-dependent regulations of CaV1.2 Ca2+ channels

Both N- and C-lobes of calmodulin are required for Ca2+-dependent regulations of CaV1.2 Ca2+ channels
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CaV1.2 Ca2 通道的 Ca2 依赖性调节需要钙调蛋白的 N 叶和 C 叶

DOI:
10.1016/j.bbrc.2009.11.171
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发表时间:
2010-01-08
影响因子:
3.1
通讯作者:
Kameyama, Masaki
Kameyama, Masaki
中科院分区:
生物学4区
文献类型:
--
作者:
Guo, Feng;Minobe, Etsuko;Kameyama, Masaki

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我们研究了CaM突变体CaM12和CaM34的浓度依赖性和Ca2+依赖性效应,其中Ca2+结合其N-叶和c -叶分别在豚鼠心肌细胞的Ca(V)1.2 Ca2+通道上被内向外膜片钳消除。CaM12和CaM34 (0.7 ~ 10 μ M)施用3mm ATP后均产生通道活性。浓度-响应曲线呈钟形,与野生型CaM相似。然而,随着[Ca2+]的增加,曲线没有明显的左移,这表明CaM的两个功能叶都是Ca2+依赖位移所必需的。然而,CaM突变体诱导的通道活性显示Ca2+依赖性降低,这表明除了CaM之外还存在Ca2+传感器。这些结果表明,Ca(V)1.2 Ca2+通道的Ca2+依赖性调节需要CaM的N-叶和c -叶。(C) 2009爱思唯尔公司版权所有。
We investigated the concentration- and Ca2+-dependent effects of CaM mutants, CaM12 and CaM34, in which Ca2+-binding to its N- and C-lobes was eliminated, respectively, on the Ca(V)1.2 Ca2+ channel by inside-out patch clamp in guinea-pig cardiomyocytes. Both CaM12 and CaM34 (0.7-10 mu M) applied with 3 mM ATP produced channel activity after "rundown". Concentration-response curves were bell-shaped, similar to that for wild-type CaM. However, there was no obvious leftward shift of the curves by increasing [Ca2+], suggesting that both functional lobes of CaM were necessary for the Ca2+-dependent shift. However, channel activity induced by the CaM mutants showed Ca2+-dependent decrease, implying a Ca2+ sensor existing besides CaM. These results suggest that both N- and C-lobes of CaM are required for the Ca2+-dependent regulations of Ca(V)1.2 Ca2+ channels. (C) 2009 Elsevier Inc. All rights reserved.