title: The role of the calcium transporter protein plasma membrane calcium ATPase PMCA2 in cerebellar Purkinje neuron function.
abstract: Genetic deletion of the plasma membrane calcium ATPase type 2 (PMCA2), a calcium transporter protein, is associated with an overtly ataxic phenotype in mice. PMCA2 is expressed at high levels in cerebellar Purkinje neurons (PNs) where functional integrity is essential for normal cerebellar function. Indeed, loss of PN function accompanies cerebellar ataxia in humans and mouse models. In the ataxic PMCA2 knockout (PMCA2-/-) mouse the ability of the PNs to control their cytosolic calcium levels was severely impaired; basal calcium levels were high and calcium recovery kinetics slow. Whole cell patch clamp recordings from PMCA2-/- PNs revealed that they possessed hyperpolarised membrane potentials, reduced frequency and increased irregularity of spontaneous action potential firing, curtailed complex spikes and sustained calcium-dependent outward K+ currents. We propose that these alterations limit pathological excursions in PN cytosolic calcium as an aid to survival but that they are insufficient to prevent loss of functional cerebellar output.
authors.affiliation: Department of Physiology, University of Otago, Dunedin, New Zealand. ruth.empson@otago.ac.nz
authors.forename: R M
authors.initials: RM
authors.lastname: Empson
authors.forename: W
authors.initials: W
authors.lastname: Akemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Knöpfel
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology*; D004558:Electric Stimulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques / Q000379:methods; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*
chemical_list: D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse; D002118:Calcium