TY - JOUR T1 - Robust Pacemaking in Substantia Nigra Dopaminergic Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11011 LP - 11019 DO - 10.1523/JNEUROSCI.2519-09.2009 VL - 29 IS - 35 AU - Jaime N. Guzman AU - Javier Sánchez-Padilla AU - C. Savio Chan AU - D. James Surmeier Y1 - 2009/09/02 UR - http://www.jneurosci.org/content/29/35/11011.abstract N2 - 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. ER -