6-Hydroxy dopamine lesions block a tolbutamide-sensitive K+ conductance in the guinea-pig substantia nigra.

A population of neurons in the anterior substantia nigra pars compacta of the guinea-pig display an outward K+ conductance, which can be activated by a brief period of hypoxia, and blocked in a dose-dependent manner by tolbutamide (100-500 microns): these features are those of an ATP-sensitive K+ channel (KATP). Typically hyperpolarisation of the cell is accompanied by a mean decrease in input resistance (IR) of 41.29 +/- 3.69 M omega (SEM), a mean decrease in resting membrane potential (RMP) of 8.58 +/- 2.41 mV and a cessation of action potential generation. These cells do not show positive immunoreactivity for tyrosine hydroxylase (TH), but they are present in slices that contain TH and release dopamine (DA). Given the intimacy of these cells with nigral DA systems, and given the fact that they have D2 receptors and respond to dopaminergic (DAergic) agents, it was of interest to see if lesions of DAergic neurons had any effect on the above response. The neurotoxin 6-hydroxy dopamine (6-OHDA) was injected into the median forebrain bundle to destroy the DAergic neurons of the nigrostriatal pathway. Unilateral lesion of this pathway produced a significant reduction in the above conductance, in the lesioned substantia nigra pars compacta (SNpc) (mean IR decrease of only 17.99 +/- 4.44 M omega (and a mean RMP decrease of 1.40 +/- 1.76 mV), whilst the hypoxia induced change in potential on the non-lesioned side was still marked and indistinguishable from that in control animals. The KATP channel would therefore appear to be under the influence of the DAergic neurons of the SNpc.