Cerebellar slice cultures from mice lacking the P/Q calcium channel: electroresponsiveness of Purkinje cells

doi:10.1016/S0304-3940(02)00962-X

Neuroscience Letters

Volume 333, Issue 1, 15 November 2002, Pages 64-68

https://doi.org/10.1016/S0304-3940(02)00962-X Get rights and content

Abstract

To investigate the role of P/Q type Ca²⁺ channels in determining the firing pattern of Purkinje cells (PCs) we compared the somatically evoked discharge of action potentials (APs) in PCs from 3 to 4 week old cerebellar slice cultures obtained with ataxic mice lacking α_1A-subunit (α^−/−) and with normal mice (non-ataxic α^+/− or α^+/+) using the whole-cell configuration of the patch-clamp recording method. Whereas evoked responses of PCs in normal mice were mainly fast APs, those of PCs from ataxic mice were mainly low-threshold Ca²⁺ spikes (LTS). Furthermore, a sustained plateau potential due to the activation of cadmium sensitive Ca²⁺ conductances was not observed in PCs from ataxic mice by blocking K⁺ channels. These results confirm that P/Q Ca²⁺ channels elicit Ca²⁺-dependent plateau potentials and control the propagation of the dendritic LTS to the soma.

Section snippets

Acknowledgements

The authors thank Prof. B. Gähwiler for comments and suggestions on this manuscript, Drs Y. Bailly and J.L. Dupont for making the immunohistochemical pictures, Dr N. Grant for reading the manuscript. This work was supported by the FRM (grant for P. Cavelier, FDT 2001 121 4020/2).

References (17)

J.L. Bossu et al.
Calcium currents in rat cerebellar Purkinje cells maintained in culture
Neuroscience
(1989)
B.H. Gähwiler
Organotypic monolayer cultures of nervous tissue
J. Neurosci. Methods
(1981)
G. Stuart et al.
Initiation and spread of sodium action potentials in cerebellar Purkinje cells
Neuron
(1994)
G. Stuart et al.
Action potential initiation and back propagation in neurons of the mammalian CNS
Trends Neurosci.
(1997)
P. Cavelier et al.
Control of the propagation of dendritic low-threshold Ca²⁺ spikes in Purkinje cells from rat cerebellar slice cultures
J. Physiol.
(2002)
L.S. Dove et al.
Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice
J. Neurosci.
(1998)
J. Doyle et al.
Mutation in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice
Mamm. Genome
(1997)
S. Hagiwara et al.
Calcium channel
Annu. Rev. Neurosci.
(1981)

There are more references available in the full text version of this article.

Cited by (8)

Caytaxin deficiency disrupts signaling pathways in cerebellar cortex
2007, Neuroscience
Citation Excerpt :
The tottering mouse, for example, exhibits paroxysmal dystonia that is precipitated by stress (Fureman et al., 2002). It is well-known that the P/Q-type calcium channel plays a critical role in the response of Purkinje cells to afferent inputs (Cavelier et al., 2002). Presumably, mutations of cerebellar P/Q-type calcium channels impair the ability of Purkinje cells to properly integrate parallel and climbing fiber inputs (Jun et al., 1999).
The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as sites of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time reverse transcriptase-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and plasma membrane calcium-dependent ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex.
Function and dysfunction of synaptic calcium channels: Insights from mouse models
2005, Current Opinion in Neurobiology
In the past few years several spontaneous or engineered mouse models with mutations in Ca²⁺ channel genes have become available, providing a powerful approach to defining Ca²⁺ channel function in vivo. There have been recent advances in outlining the phenotypes and in the functional analysis of mouse models with mutations in genes encoding the pore-forming subunits of Ca_V2.1 (P/Q-type), Ca_V2.2 (N-type) and Ca_V2.3 (R-type) Ca²⁺ channels, the channels involved in controlling neurotransmitter release at mammalian synapses. These data indicate that Ca_V2.1 channels have a dominant and efficient specific role in initiating fast synaptic transmission at central excitatory synapses in vivo, and suggest that the Ca_V2.1 channelopathies are primarily synaptic diseases. The different disorders probably arise from disruption of neurotransmission in specific brain regions: the cortex in the case of migraine, the thalamus in the case of absence epilepsy and the cerebellum in the case of ataxia.
Organotypic cultures of cerebellar slices as a model to investigate demyelinating disorders
2017, Expert Opinion on Drug Discovery
Contributions of T-type voltage-gated calcium channels to postsynaptic calcium signaling within purkinje neurons
2012, Cerebellum
Lobule-specific membrane excitability of cerebellar Purkinje cells
2012, Journal of Physiology
Altered Purkinje cell responses and calmodulin expression in the spontaneously ataxic mouse, Pogo
2011, European Journal of Neuroscience

View all citing articles on Scopus

View full text

Article preview

Neuroscience Letters

Abstract

Section snippets

Acknowledgements

References (17)

Calcium currents in rat cerebellar Purkinje cells maintained in culture

Neuroscience

Organotypic monolayer cultures of nervous tissue

J. Neurosci. Methods

Initiation and spread of sodium action potentials in cerebellar Purkinje cells

Neuron

Action potential initiation and back propagation in neurons of the mammalian CNS

Trends Neurosci.

Control of the propagation of dendritic low-threshold Ca²⁺ spikes in Purkinje cells from rat cerebellar slice cultures

J. Physiol.

Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice

J. Neurosci.

Mutation in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice

Mamm. Genome

Calcium channel

Annu. Rev. Neurosci.

Cited by (8)

Caytaxin deficiency disrupts signaling pathways in cerebellar cortex

Function and dysfunction of synaptic calcium channels: Insights from mouse models

Organotypic cultures of cerebellar slices as a model to investigate demyelinating disorders

Contributions of T-type voltage-gated calcium channels to postsynaptic calcium signaling within purkinje neurons

Lobule-specific membrane excitability of cerebellar Purkinje cells

Altered Purkinje cell responses and calmodulin expression in the spontaneously ataxic mouse, Pogo

Cerebellar slice cultures from mice lacking the P/Q calcium channel: electroresponsiveness of Purkinje cells

Abstract

Section snippets

Acknowledgements

Neuroscience

J. Neurosci. Methods

Neuron

Trends Neurosci.

Control of the propagation of dendritic low-threshold Ca2+ spikes in Purkinje cells from rat cerebellar slice cultures

J. Physiol.

Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice

J. Neurosci.

Mutation in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice

Mamm. Genome

Calcium channel

Annu. Rev. Neurosci.

Control of the propagation of dendritic low-threshold Ca²⁺ spikes in Purkinje cells from rat cerebellar slice cultures