ArticleThe Journal of physiology2010
Reduced expression of the Ca(2+) transporter protein PMCA2 slows Ca(2+) dynamics in mouse cerebellar Purkinje neurones and alters the precision of motor coordination.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- CaNature communications · 2025Article
- Methylome and transcriptome joint analyses identify differentially expressed genes based on purebred and crossbred Tianjin-monkey Chicken.Animal biotechnology · 2024Article
- Pre-ataxic loss of intrinsic plasticity and motor learning in a mouse model of SCA1.Brain : a journal of neurology · 2023Article
- Article
- Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases.International journal of molecular sciences · 2021Review
- Estrogen receptors in pain modulation: cellular signaling.Biology of sex differences · 2021Review
- The Puzzling Role of Neuron-Specific PMCA Isoforms in the Aging Process.International journal of molecular sciences · 2019Review
- Calcium Dyshomeostasis Alters CCL5 Signaling in Differentiated PC12 Cells.BioMed research international · 2019Article
- A link between plasma membrane calcium ATPase 2 (PMCA2), estrogen and estrogen receptor α signaling in mechanical pain.Scientific reports · 2018Article
- Evidence for a role of plasma membrane calcium pumps in neurodegenerative disease: Recent developments.Neuroscience letters · 2018Review
- A positive feedback loop linking enhanced mGluR function and basal calcium in spinocerebellar ataxia type 2.eLife · 2017Article
- Cellular and circuit mechanisms underlying spinocerebellar ataxias.The Journal of physiology · 2016Review
- Regulation of GAP43/calmodulin complex formation via calcineurin-dependent mechanism in differentiated PC12 cells with altered PMCA isoforms composition.Molecular and cellular biochemistry · 2015Article
- A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.The Journal of biological chemistry · 2015Article
- Neuronal calcium signaling: function and dysfunction.Cellular and molecular life sciences : CMLS · 2014Review
- Enhanced synaptic inhibition in the cerebellar cortex of the ataxic PMCA2(-/-) knockout mouse.Cerebellum (London, England) · 2013Article
- A new Atp2b2 deafwaddler allele, dfw(i5), interacts strongly with Cdh23 and other auditory modifiers.Hearing research · 2013Article
- Functional contributions of the plasma membrane calcium ATPase and the sodium-calcium exchanger at mouse parallel fibre to Purkinje neuron synapses.Pflugers Archiv : European journal of physiology · 2013Article
- Plasma membrane calcium ATPases as novel candidates for therapeutic agent development.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2013Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebellar Purkinje neurones (PNs) express high levels of the plasma membrane calcium ATPase, PMCA2, a transporter protein critical for the clearance of calcium from excitable cells. Genetic deletion of one PMCA2 encoding gene in heterozygous PMCA2 knock-out (PMCA2(+/-) mice enabled us to determine how PMCA2 influences PN calcium regulation without the complication of the severe morphological changes associated with complete PMCA2 knock-out (PMCA2(-/-) in these cells. The PMCA2(+/-) cerebellum expressed half the normal levels of PMCA2 and this nearly doubled the time taken for PN dendritic calcium transients to recover (mean fast and slow recovery times increased from 70 ms to 110 ms and from 600 ms to 1100 ms). The slower calcium recovery had distinct consequences for PMCA2(+/-) PN physiology. The PNs exhibited weaker climbing fibre responses, prolonged outward Ca(2+)-dependent K(+) current (mean fast and slow recovery times increased from 136 ms to 192 ms and from 595 ms to 1423 ms) and a slower mean frequency of action potential firing (7.4 Hz compared with 15.8 Hz). Our findings were consistent with prolonged calcium accumulation in the cytosol of PMCA2(+/-) Purkinje neurones. Although PMCA2(+/-) mice exhibited outwardly normal behaviour and little change in their gait pattern, when challenged to run on a narrow beam they exhibited clear deficits in hindlimb coordination. Training improved the motor performance of both PMCA2(+/-) and wild-type mice, although PMCA2(+/-) mice were always impaired. We conclude that reduced calcium clearance perturbs calcium dynamics in PN dendrites and that this is sufficient to disrupt the accuracy of cerebellar processing and motor coordination.
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