Hindawi Publishing Corporation Neural Plasticity Volume 2013, Article ID 321685, 7 pages http://dx.doi.org/10.1155/2013/321685 Research Article The Plasma Membrane Ca 2+ -ATPase2 (PMCA2) Is Involved in the Regulation of Purkinje Cell Dendritic Growth in Cerebellar Organotypic Slice Cultures Pradeep Sherkhane and Josef P. Kapfhammer Anatomical Institute, Department of Biomedicine, University of Basel, Pestalozzistraße 20, 4056 Basel, Switzerland Correspondence should be addressed to Josef P. Kaphammer; josef.kaphammer@unibas.ch Received 4 July 2013; Revised 30 August 2013; Accepted 3 September 2013 Academic Editor: Rachel M. Sherrard Copyright © 2013 P. Sherkhane and J. P. Kaphammer. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purkinje cells are the principal neurons of the cerebellar cortex and have an extensive and elaborate dendritic tree. Chronic activation of type I metabotropic glutamate receptors inhibits Purkinje cell dendritic growth in organotypic cerebellar slice cultures. his efect is mediated by calcium inlux through P/Q-type and T-type Ca 2+ channels. We have now studied the role of the plasma membrane Ca 2+ -ATPase2 (PMCA2), a major calcium extrusion pump, for Purkinje cell dendritic development. We found that PMCA2 is strongly expressed in the plasma membrane and dendritic spines of Purkinje cells in organotypic slice cultures compatible with a role for controlling the local dendritic calcium equilibrium. Inhibition of PMCA2 activity by carboxyeosin resulted in a moderate reduction of Purkinje cell dendritic tree size indicating that the extrusion of calcium by PMCA2 is important for maintaining the dendritic calcium concentration and controlling dendritic growth. When inhibition of PMCA2 was combined with stimulation of type I metabotropic glutamate receptors, it partially rescued dendritic morphology. his protection can be explained by a compensatory inactivation of voltage-gated calcium channels in Purkinje cells ater PMCA2 inhibition. Our results demonstrate that PMCA2 activity is an important regulator of the dendritic calcium equilibrium controlling Purkinje cell dendritic growth. 1. Introduction Purkinje cells are the principal neurons of the cerebellar cortex and have an extensive and elaborate dendritic tree. hey receive excitatory synaptic input from granule cell derived parallel ibers and inferior olive derived climbing ibers. he development of the Purkinje cell dendritic tree is controlled by a variety of intrinsic and extrinsic signals [1, 2]. We have previously shown that chronic activation of either type I metabotropic glutamate receptors (mGluR1s) or pro- tein kinase C (PKC) in organotypic cerebellar slice cultures severely inhibits the growth and development of the Purkinje cell dendrites [3–5]. he stunted dendritic growth seen ater mGluR1 or PKC stimulation is partially rescued by pharma- cological blockade of P/Q-type and T-type Ca 2+ channels, indicating that activation of these channels mediating Ca 2+ inlux contributes to the inhibition of Purkinje cell dendritic growth [6]. Besides the inlux of calcium through voltage- dependent channels, calcium clearance mechanisms also afect the calcium equilibrium in Purkinje cells [7–9]. he plasma membrane Ca 2+ -ATPase2 (PMCA2) is reported to be involved in extrusion of calcium and cerebellar synapse func- tion [7]. PMCA2 belongs to the family of P-type primary ion transport ATPases characterized by the formation of aspartyl phosphate intermediate during an ATP hydrolysis reaction cycle. Of the known PMCA variants, PMCA1 and PMCA4 are expressed ubiquitously whereas PMCA2 and PMCA3 are expressed prevalently in the central nervous systems. he PMCA2 isoform is highly expressed in the cerebellum, partic- ularly in Purkinje cell dendrites and dendritic spines [10, 11]. Two spontaneous mouse mutants with a loss of function