DOSE-DEPENDENT ACTIVATION AND BLOCK BY BISG10, A K+ CHANNEL BLOCKER, OF MOUSE AND FROG SKELETAL-MUSCLE K-ATP CHANNELS

The effects of a K+ channel blocker, bisG10, were examined on ATP-sensitive K+ (K-ATP) channels in membrane patches excised from mammalian and amphibian skeletal muscle fibres using the patch-clamp technique. At micromolar concentrations, bisG10, added on the intracellular side, induced a strong, reversible, flickery block of K-ATP channels. BisG10, added on the extracellular side, was about 100-fold less potent at inhibiting channel activity. At 10 nM, intracellular bisG10 increased K-ATP channel activity. This activation was independent of the presence of internal ATP or Mg2+. The inhibitory effect of bisG10 most likely arose from open-channel block whereas activation could result from more complex, indirect interactions.