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. This effect is mediated by calcium influx through P/Q-type and T-type Ca2+ channels. We have now studied the role of the plasma membrane Ca2+-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. This protection can be explained by a compensatory inactivation of voltage-gated calcium channels in Purkinje cells after 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. They receive excitatory synaptic input from granule cell derived parallel fibers and inferior olive derived climbing fibers. The 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 protein kinase C (PKC) in organotypic cerebellar slice cultures severely inhibits the growth and development of the Purkinje cell dendrites [3–5]. The stunted dendritic growth seen after mGluR1 or PKC stimulation is partially rescued by pharmacological blockade of P/Q-type and T-type Ca2+ channels, indicating that activation of these channels mediating Ca2+ influx contributes to the inhibition of Purkinje cell dendritic growth [6]. Besides the influx of calcium through voltage-dependent channels, calcium clearance mechanisms also affect the calcium equilibrium in Purkinje cells [7–9]. The plasma membrane Ca2+-ATPase2 (PMCA2) is reported to be involved in extrusion of calcium and cerebellar
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