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Journal of Neuroscience, Vol 16, 1-9, Copyright © 1996 by Society for Neuroscience
A strongly inwardly rectifying K+ channel that is sensitive to ATP
A Collins, MS German, YN Jan, LY Jan and B Zhao
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143-0724, USA.
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.
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