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The Journal of Neuroscience, September 2, 2009, 29(35):11011-11019; doi:10.1523/JNEUROSCI.2519-09.2009

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Neurobiology of Disease
Robust Pacemaking in Substantia Nigra Dopaminergic Neurons

Jaime N. Guzman, ^* Javier Sánchez-Padilla, ^* C. Savio Chan, and D. James Surmeier

Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611

Correspondence should be addressed to Dr. D. James Surmeier, Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611. Email: j-surmeier{at}northwestern.edu

Dopaminergic neurons of the substantia nigra pars compacta are autonomous pacemakers. This activity is responsible for the sustained release of dopamine necessary for the proper functioning of target structures, such as the striatum. Somatodendritic L-type Ca²⁺ channels have long been viewed as important, if not necessary, for this activity. The studies reported here challenge this viewpoint. Using a combination of optical and electrophysiological approaches in brain slices, it was found that antagonism of L-type Ca²⁺ channel effectively stopped dendritic Ca²⁺ oscillations but left autonomous pacemaking unchanged. Moreover, damping intracellular Ca²⁺ oscillations with exogenous buffer had little effect on pacemaking rate. Although not necessary for pacemaking, L-type channels helped support pacemaking when challenged with cationic channel blockers. Simulations suggested that the insensitivity to antagonism of L-type channels reflected the multichannel nature of the pacemaking process. The robustness of pacemaking underscores its biological importance and provides a framework for understanding how therapeutics targeting L-type Ca²⁺ channels might protect dopaminergic neurons in Parkinson's disease without compromising their function.

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Received May 30, 2009; revised July 13, 2009; accepted July 27, 2009.

Correspondence should be addressed to Dr. D. James Surmeier, Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611. Email: j-surmeier{at}northwestern.edu

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