1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
2. Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, Chicago, Illinois 60064, USA
3. Present address: BCTU, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Correspondence to: D. James Surmeier¹ Correspondence and requests for materials should be addressed to D.J.S. (Email: j-surmeier@northwestern.edu).

Abstract

Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca_v1.3 Ca²⁺ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca_v1.3 Ca²⁺ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.

1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
2. Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, Chicago, Illinois 60064, USA
3. Present address: BCTU, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Correspondence to: D. James Surmeier¹ Correspondence and requests for materials should be addressed to D.J.S. (Email: j-surmeier@northwestern.edu).

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.