Ruth M Empson, MA, PhD, Department of Physiology, Brain Health and Repair Research Centre, University of Otago, Dunedin, 9001, New Zealand. ruth.empson@stonebow.otago.ac.nz
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World J Biol Chem. May 26, 2010; 1(5): 95-102 Published online May 26, 2010. doi: 10.4331/wjbc.v1.i5.95
Contribution of plasma membrane Ca2+ ATPase to cerebellar synapse function
Helena Huang, Raghavendra Y Nagaraja, Molly L Garside, Walther Akemann, Thomas Knöpfel, Ruth M Empson
Helena Huang, Raghavendra Y Nagaraja, Ruth M Empson, Department of Physiology, Brain Health and Repair Research Centre, University of Otago, Dunedin, 9001, New Zealand
Molly L Garside, School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, TW20 0EX, United Kingdom
Walther Akemann, Thomas Knöpfel, Ruth M Empson, Laboratory for Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Wako-ishi, Saitama, 351-0198, Japan
Author contributions: Huang H, Nagaraja RY, Garside ML, Akemann W and Empson RM performed research; Huang H and Nagaraja RY made equal contributions; Empson RM and Knöpfel T wrote the article.
Supported by An Health Research Council-Japanese Society for the Promotion of Science fellowship and the Neurological Foundation of New Zealand (Empson RM and Nagaraja RY), a British Biological and Biotechnology Research Council award (Empson RM and Garside ML), a Department of Physiology MSc studentship (Huang H) and RIKEN intramural funding (Knöpfel T)
Correspondence to: Ruth M Empson, MA, PhD, Department of Physiology, Brain Health and Repair Research Centre, University of Otago, Dunedin, 9001, New Zealand. ruth.empson@stonebow.otago.ac.nz
Telephone: +64-3-4797323 Fax: +64-3-4797464
Received: May 10, 2010 Revised: May 17, 2010 Accepted: May 20, 2010 Published online: May 26, 2010
Abstract
The cerebellum expresses one of the highest levels of the plasma membrane Ca2+ ATPase, isoform 2 in the mammalian brain. This highly efficient plasma membrane calcium transporter protein is enriched within the main output neurons of the cerebellar cortex; i.e. the Purkinje neurons (PNs). Here we review recent evidence, including electrophysiological and calcium imaging approaches using the plasma membrane calcium ATPase 2 (PMCA2) knockout mouse, to show that PMCA2 is critical for the physiological control of calcium at cerebellar synapses and cerebellar dependent behaviour. These studies have also revealed that deletion of PMCA2 throughout cerebellar development in the PMCA2 knockout mouse leads to permanent signalling and morphological alterations in the PN dendrites. Whilst these findings highlight the importance of PMCA2 during cerebellar synapse function and development, they also reveal some limitations in the use of the PMCA2 knockout mouse and the need for additional experimental approaches including cell-specific and reversible manipulation of PMCAs.
