Membrane stretch affects gating modes of a skeletal muscle sodium channel.

Membrane stretch affects gating modes of a skeletal muscle sodium channel.
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膜拉伸影响骨骼肌钠通道的门控模式。

DOI:
10.1016/s0006-3495(99)76930-4
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发表时间:
1999
影响因子:
3.4
通讯作者:
C. Morris
C. Morris
中科院分区:
生物学3区
文献类型:
--
作者:
I. Tabarean;P. Juranka;C. Morris

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正如非洲爪蟾细胞所预期的那样,从细胞贴附斑块记录的人类骨骼肌 Na+ 通道的 α 亚基产生了两种电流成分,它们在 0.2Hz 刺激期间稳定数十分钟。然而,在持续拉伸的几秒钟内,较慢的成分开始减少,并且根据拉伸强度,在 1-3 分钟内消失。与此同时,电流增加得更快。由此产生的快速电流动力学和电压敏感性与 1) 10Hz 去极化后留下的快速成分和 2) 当 α 亚基与人 β1 亚基共表达时占主导地位的快速成分没有区别。虽然高频去极化引起的慢电流损失是可逆的,但拉伸引起的慢到快的转换是不可逆的。通过使用无吸力形成的千兆欧姆密封(其中最初不存在快速门控)证实了拉伸将单个α亚基群从异常慢速门控模式转变为真正的快速门控模式的结论。对于脑 Na+ 通道,G 蛋白与通道 α 亚基共表达会产生缓慢的门控。因为拉伸亚基和β1亚基都诱导了快速门控模式,也许它们是通过最大限度地减少α亚基与G蛋白或卵母细胞膜中其他调节分子的相互作用来实现的。由于卵母细胞分子可能参与其中,Na+通道α亚基是否直接或继发地对双层张力敏感仍有待确定。
Theαsubunit of the human skeletal muscle Na+channel recorded from cell-attached patches yielded, as expected forXenopusoocytes, two current components that were stable for tens of minutes during 0.2Hz stimulation. Within seconds of applying sustained stretch, however, the slower component began decreasing and, depending on stretch intensity, disappeared in 1–3min. Simultaneously, the faster current increased. The resulting fast current kinetics and voltage sensitivity were indistinguishable from the fast components 1) left after 10Hz depolarizations, and 2) that dominated whenαsubunit was co-expressed with humanβ1 subunit. Although high frequency depolarization-induced loss of slow current was reversible, the stretch-induced slow-to-fast conversion was irreversible. The conclusion that stretch converted a single population ofαsubunits from an abnormal slow to a bona fide fast gating mode was confirmed by using gigaohm seals formed without suction, in which fast gating was originally absent. For brain Na+channels, co-expressing G proteins with the channelαsubunit yields slow gating. Because both stretch andβ1 subunits induced the fast gating mode, perhaps they do so by minimizingαsubunit interactions with G proteins or with other regulatory molecules available in oocyte membrane. Because of the possible involvement of oocyte molecules, it remains to be determined whether the Na+channelαsubunit was directly or secondarily susceptible to bilayer tension.
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