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A McGroarty

Publications and source records attributed to A McGroarty.

4 recordsLinked to original sources
PubMed1997

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.

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PubMed1996

Blockade of dopamine storage, but not of dopamine synthesis, prevents activation of a tolbutamide-sensitive K+ channel in the guinea-pig substantia nigra.

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.

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