The substantia nigra has one of the highest levels of
ATP-sensitive K+ channel in the brain. Since this channel is controlled by cell metabolism, the aim of this study was to see how closely it is associated with nigral
dopamine systems, which are decreased in
Parkinson's disease. In a sub-population of neurons within the rostral substantia nigra pars compacta of the guinea-pig, a brief period of
hypoxia resulted in a
tolbutamide (100-500 microM) sensitive hyperpolarisation [input resistance (IR) decrease from 144.88 +/- 14.04 M omega pre-
hypoxia to 105.91 +/- 13.25 M omega during
hypoxia]. Maximal blockade of this decrease was seen in presence of 500 microns
tolbutamide [IR decrease only from 161.35 +/- 32.82 M omega to 155.02 +/- 34.29 M omega].
Reserpine (which depletes
dopamine stores) but not
alpha-methyl-para-tyrosine (which decreases de novo synthesis of
dopamine) caused a marked attenuation of this hyperpolarisation [IR decrease only from 163.32 +/- 44.42 M omega pre-
hypoxia to 154.42 +/- 50.97 M omega during
hypoxia]. This observation suggests that blockade of
dopamine storage, but not of de novo synthesis, leads to a loss of responsiveness of certain mid-brain neurons to
hypoxia, rendering them potentially more susceptible to subsequent degeneration. The possible link between nigral
dopamine systems and
ATP-sensitive K+ channels is discussed.