A STRONGLY INWARDLY RECTIFYING K+ CHANNEL THAT IS SENSITIVE TO ATP

We have cloned an inwardly rectifying K+ channel from the hamster insu linoma cDNA library and shown that it is inhibited by cytoplasmic ATP. The channel is 90-97% identical to the IRK3 channels cloned from othe r species, and its mRNA is found primarily in the brain. When expresse d 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 appe ar to involve ATP hydrolysis, as shown by studies of channels in excis ed inside-out membrane parches. This effect is antagonized by ADP, aga in 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.