An ether-a-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts
An ether-a-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts
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DOI：
10.1111/j.1469-7793.1998.317be.x
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发表时间：
1998-10-15
影响因子：
5.5
通讯作者：
Fischer-Lougheed, J
中科院分区：
文献类型：
--
作者：
Bijlenga, P;Occhiodoro, T;Fischer-Lougheed, J
1.人成肌细胞融合的两个早期标志是膜电位超极化和伴随的非失活延迟整流钾电流I-K（NI）的表达。该电流与大鼠ether-a-go-go（r-eag）通道诱发的外向K+电流在激活电位和单位电导范围内非常相似.结果表明，I-K（NI）的活化动力学与r-eag的活化动力学一样，依赖于保持电位和[Mg ~（2+）]（o），而I-K（NI）与r-eag的活化动力学一样，受到[Ca ~（2+）]（i）的可逆抑制.在未分化的成肌细胞中强制表达分离的人ether-a-go-go K+通道（h-eag）cDNA产生与I-K（NI）显著相似的单通道和全细胞电流. h-eag电流（Ih-eag）被[Ca 2 +]（i）的升高可逆地抑制，并且激活动力学取决于保持电位和[Mg 2 +]（o）。h-eag的强制表达使未分化的成肌细胞从-9 mV超极化至-50 mV，这是I h-eag和I-K（NI）激活的阈值。同样，I-K（NI）密度越高，融合成肌细胞静息电位越超极化。它的结论是，h-eag构成的通道I-K（NI）的基础上，它有助于融合能力成肌细胞的超极化。据我们所知，这是第一次证明哺乳动物eag K+通道的生理作用。
1. Two early signs of human myoblast commitment to fusion are membrane potential hyperpolarization and concomitant expression of a non-inactivating delayed rectifier K+ current, I-K(NI). This current closely resembles the outward K+ current elicited by rat ether-a-go-go (r-eag) channels in its range of potential for activation and unitary conductance.2. It is shown that activation kinetics of I-K(NI), like those of r-eag, depend on holding potential and on [Mg2+](o), and that I-K(NI), like r-eag, is reversibly inhibited by a rise in [Ca2+](i).3. Forced expression of an isolated human ether-a-go-go K+ channel (h-eag) cDNA in undifferentiated myoblasts generates single-channel and whole-cell currents with remarkable similarity to I-K(NI).4. h-eag current (Ih-eag) is reversibly inhibited by a rise in [Ca2+](i), and the activation kinetics depend on holding potential and [Mg2+](o).5. Forced expression of h-eag hyperpolarizes undifferentiated myoblasts from -9 to -50 mV, the threshold for the activation of both I h-eag and I-K(NI). Similarly, the higher the density of I-K(NI), the more hyperpolarized the resting potential of fusion-competent myoblasts.6. It is concluded that h-eag constitutes the channel underlying I-K(NI), and that it contributes to the hyperpolarization of fusion-competent myoblasts. To our knowledge, this is the first demonstration of a physiological role for a mammalian eag K+ channel.