Degeneration of dopaminergic neurones

Parkinson's disease consists in the degeneration of dopaminergic neurones from the substantia nigra pars compacta. Knowing why dopaminergic neurones degenerate would be an important step toward the cure. Two recent articles provide some clues (Avshalumov et al., 2005; Liss et al., 2005).
The article by Liss et al., point out that in Parkinson's disease other dopaminergic neurones, such as those from the ventral tegmental area (VTA) are spared, and they examined the differences between the two populations accordingly. They noticed that the VTA neurones have a smaller ATP-dependent K current (Kir-6.2), and the calcium-binding protein calbinding was more frequently found there. The mouth-watering result is that removal of the Kir-6.2 turns the dopaminergic cells insensitive to MPTP (a substance that induces cell death that resembles Parkinson's disease). The obvious conclusion is that K-ATP is required for cell death. Then, they tried to find differences in the K-ATP channel in the two cell types (VTA and substantia nigra), but found nothing substantial. So, they concluded that "cell-specific differences in the channel regulation are expected." But we do not know what these differences are.
The second article by Ashalumlov et al., makes complementary observations. The authors recorded from dopaminergic neurones using a dye that is sensitive to hydrogen peroxide (H₂O₂). The H₂O₂ has gained a reputation for producing oxidative damage in cells. But here it activates the K-ATP channel. Using their technique, they could see the increase in H₂O₂ as the living neuron fires a train of action potentials. If they let the H₂O₂ accumulate by blocking the peroxidase enzyme, some cells hyperpolarise due to the activation of a K-ATP channel. And they found that only the cells expressing the regulatory SUR1 subunit did so.
What we learn from these two articles is that oxidative stress lead to the production of H₂O₂, which activates the K-ATP dependent channel producing cell death. One could speculate that the cells that die are those unable to hyperpolarise (i.e., those expressing SUR2), and the dopaminergic cell will keep producing H₂O₂ to dangerous level without being able to activate the K-ATP. Of course, this idea should wait for experimental verification. Stay tuned.