Collins A, German M S, Jan Y N, Jan L Y, Zhao B
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143-0724, USA.
J Neurosci. 1996 Jan;16(1):1-9. doi: 10.1523/JNEUROSCI.16-01-00001.1996.
We have cloned an inwardly rectifying K+ channel from the hamster insulinoma cDNA library and shown that it is inhibited by cytoplasmic ATP. The channel is 90.97% identical to the IRK3 channels cloned from other species, and its mRNA is found primarily in the brain. When expressed in Xenopus oocytes, the channel displays strong inward rectification typical of inward rectifiers. The channel is inhibited reversibly by physiological concentrations of ATP via a mechanism that does not appear to involve ATP hydrolysis, as shown by studies of channels in excised inside-out membrane patches. This effect is antagonized by ADP, again in the physiological range, implying that this channel is sensitive to the index of metabolic state, i.e., the intracellular [ATP]/[ADP] ratio. This channel is different from previously known ATP-sensitive K+ channels, although it may also be stimulated by MgATP, as are other ATP-sensitive K+ channels. The potential physiological significance of these ATP-dependent regulations will be discussed.
我们从仓鼠胰岛素瘤cDNA文库中克隆了一种内向整流钾通道,并证明它受到细胞质ATP的抑制。该通道与从其他物种克隆的IRK3通道有90.97%的同源性,其mRNA主要在大脑中发现。当在非洲爪蟾卵母细胞中表达时,该通道表现出内向整流器典型的强内向整流特性。如对切除的内向外膜片上的通道进行的研究所显示,该通道被生理浓度的ATP通过一种似乎不涉及ATP水解的机制可逆地抑制。这种效应在生理范围内被ADP拮抗,这意味着该通道对代谢状态指标,即细胞内[ATP]/[ADP]比值敏感。该通道与先前已知的ATP敏感性钾通道不同,尽管它也可能像其他ATP敏感性钾通道一样被MgATP刺激。将讨论这些ATP依赖性调节的潜在生理意义。