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 microM tetrodotoxin or superfusion with Ca2(+)-free medium. While glibenclamide at 30 microM and tolbutamide at 300 microM 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 on the GABA neurones of SNR and that these channels are activated in energy-depleting conditions exemplified by hypoxia.
Wu
C W
CW
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
Leung
C K
CK
Yung
W H
WH
D000818:Animals; D005905:Glyburide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D015221:Potassium Channels; D013779:Tetrodotoxin; D005905:Glyburide