ATP-independent anoxic activation of ATP-sensitive K+ channels in dorsal vagal neurons of juvenile mice in situ. 
The role of ATP in anoxic activation of ATP-sensitive K+ (KATP) channels was studied in dorsal vagal neurons of mouse brainstem slices.  In the whole-cell configuration, cyanide-induced chemical anoxia evoked within 10 s a 300-pA outward current that gave rise to a hyperpolarization of 24 mV. These responses were mimicked by nitrogen-aerated saline, rotenone or diazoxide and abolished by tolbutamide.  The cyanide-induced hyperpolarization was due to activation of 70 pS K(ATP) channels that were half-maximally blocked by 5 microM internal ATP.  Dialyzing the cells with either 1, 20 or 0 mM ATP did not, however, affect the time to onset, the kinetics or the magnitude of the cyanide-induced hyperpolarization.  Impairment of ATP consumption by ouabain, vanadate or reduced temperature had no effect either.  Thus, anoxia-induced activation of these KATP channels cannot be explained by a fall of cellular ATP or a concomitant rise of ADP.  Anoxia-related changes of the actin cytoskeleton or the composition of the plasma membrane are also not likely to be involved, as cytochalasin D did not affect the cyanide-evoked hyperpolarization and phosphatidylinositol 4,5-bisphosphate failed to decrease the ATP sensitivity of single KATP channels.  Finally, because of a lack of effects of reduced/oxidized glutathione and the oxidase blocker diphenyliodonium on the cyanide-induced hyperpolarization, cellular redox state does not appear to be involved.  Our results indicate that despite a high sensitivity to ATP in excised patches, anoxic activation of KATP channels is independent of cellular ATP.  Rather the ATP block seems to be removed as a consequence of impaired mitochondrial function.