Sulphonylureas reverse hypoxia induced K⁺-conductance increase in substantia nigra pars reticulata neurones

Membrane potentials were recorded from neuronal somata in the substantia nigra pars reticulata of the rat midbrain slice using the whole-cell patch-clamp technique. Hypoxia induced a consistent decrease in input resistance often accompanied by membrane hyperpolarization and cessation of firing. The membrane hyperpolarization was mediated by K⁺ as indicated by its reversal potential at -88 ± 9 mV, which is close to the equilibrium potential of K⁺. The hypoxic response was not sensitive to 1 μM tetrodotoxin or superfusion with Ca²⁺-free medium. While glibenclamide at 30 μM and tolbutamide at 300 μM had no effect on the resting membrane properties of the neurones, these sulphonylureas reversed the hypoxia-induced membrane hyperpolarization and restored firing. Inclusion of 2 mM of ATP in the recording pipette also prevented the hyperpolarization. These observations suggest that post-synaptic ATP-sensitive potassium channels exist the GABA neurones of SNR and that these channels are activated in energy-depleting conditions exemplified by hypoxia.