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

The effects of a K+ channel blocker, bisG10, were examined on ATP-sens itive K+ (K-ATP) channels in membrane patches excised from mammalian a nd amphibian skeletal muscle fibres using the patch-clamp technique. A t 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 i nhibiting 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 mor e complex, indirect interactions.