Effect of adenosine and intracellular GTP on K-ATP channels of mammalian skeletal muscle

We investigated the action of adenosine and GTP on K-ATP channels, using inside-out patch clamp recordings from dissociated single fibers of rat flexor digitorum brevis (FDB) skeletal muscle. In excised patches, K-ATP channels could be activated by a combination of an extracellular adenosine agonist and intracellular Mg2+-ATP and GTP or GTP-gamma-S. The activation required hydrolyzable ATP and could be partially reversed with Mg2+, suggesting that it may involve a G-protein dependent phosphorylation of K-ATP channels. We found that K channels of the rat FDB could not be activated by Mg2+-ATP alone or by Mg2+-ATP in the presence of extracellular adenosine. Patches whose channel activity had been 'rundown' by Ca2+ could not be recovered by adenosine, GTP or Mg2+-ATP. K-ATP channels activated by adenosine receptor agonists had a similar ATP sensitivity to those under control conditions; but adenosine appears to be able to switch these K-ATP channels from an inactive to an active mode.