SULFONYLUREAS REVERSE HYPOXIA-INDUCED K-CONDUCTANCE INCREASE IN SUBSTANTIA-NIGRA PARS RETICULATA NEURONS()

MEMBRANE potentials were recorded from neuronal somata in the substant ia nigra pars reticulata of the rat midbrain slice using the whole-cel l patch-clamp technique. Hypoxia induced a consistent decrease in inpu t resistance often accompanied by membrane hyperpolarization and cessa tion of firing. The membrane hyperpolarization was mediated by K+ as i ndicated by its reversal potential at -88 +/- 9 mV, which is close to the equilibrium potential of K+. The hypoxic response was not sensitiv e to 1 mu M tetrodotoxin or superfusion with Ca2+-free medium. While g libenclamide at 30 mu M and tolbutamide at 300 mu M had no effect on t he resting membrane properties of the neurones, these sulphonylureas r eversed the hypoxia-induced membrane hyperpolarization and restored fi ring. 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 on the GABA neurones of SNR and that these channels are activated in energy-depleting conditions exem plified by hypoxia.