PubMed 25297088

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.3

Title: Mutant α-synuclein enhances firing frequencies in dopamine substantia nigra neurons by oxidative impairment of A-type potassium channels.

Authors: Mahalakshmi Subramaniam, Daniel Althof, Suzana Gispert, Jochen Schwenk, Georg Auburger, Akos Kulik, Bernd Fakler, Jochen Roeper

Journal, date & volume: J. Neurosci., 2014 Oct 8 , 34, 13586-99

PubMed link:

Parkinson disease (PD) is an α-synucleinopathy resulting in the preferential loss of highly vulnerable dopamine (DA) substantia nigra (SN) neurons. Mutations (e.g., A53T) in the α-synuclein gene (SNCA) are sufficient to cause PD, but the mechanism of their selective action on vulnerable DA SN neurons is unknown. In a mouse model overexpressing mutant α-synuclein (A53T-SNCA), we identified a SN-selective increase of in vivo firing frequencies in DA midbrain neurons, which was not observed in DA neurons in the ventral tegmental area. The selective and age-dependent gain-of-function phenotype of A53T-SCNA overexpressing DA SN neurons was in part mediated by an increase of their intrinsic pacemaker frequency caused by a redox-dependent impairment of A-type Kv4.3 potassium channels. This selective enhancement of "stressful pacemaking" of DA SN neurons in vivo defines a functional response to mutant α-synuclein that might be useful as a novel biomarker for the "DA system at risk" before the onset of neurodegeneration in PD.