Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau

Bobik, Marketta; Ellisman, Mark H.; Rudy, Bernardo; Martone, Maryann E.

doi:10.1016/j.brainres.2004.07.088

Cited by 35 publications

(33 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this regard, the lack of Na V (Laube et al, 1996;Fig. 4 D, E) and predominant localization of Shaker-type (K V 1.1 and K V 1.2) potassium channels together with their scaffolding protein PSD-95 (Laube et al, 1996;Bobik et al, 2004;Fig. 9) may prevent active impulse conduction in the pinceau formation.…”

Section: Discussionmentioning

confidence: 99%

“…BC axons make direct contact with the AIS, but synaptic contacts are rare compared with the hippocampus and neocortex. Instead, the AIS is mostly covered with astrocytic processes in PCs (Palay, 1974;Somogyi and Hamori, 1976;Bobik et al, 2004;Sotelo, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Distinct molecular-anatomical organizations in the pinceau formation, such as high K V expression, absence of Na V , and developed septatelike junctions (Sotelo and Llinás, 1972;Wang et al, 1994;Laube et al, 1996;Bobik et al, 2004), are thought to support the hypothesized electrical inhibition. However, findings regarding GABAergic inhibition are still fragmented and inconclusive.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation

Iwakura

Uchigashima²,

Miyazaki³

et al. 2012

Journal of Neuroscience

View full text Add to dashboard Cite

The axon initial segment (AIS) of cerebellar Purkinje cells (PCs) is embraced by ramified axons of GABAergic basket cells (BCs) called the pinceau formation. This unique structure has been assumed to be a device for the modulation of PC outputs through electrical and/or GABAergic inhibition. Electrical inhibition is supported by enriched potassium channels, absence of sodium channels, and developed septate-like junctions between BC axons. The neurochemical basis for GABAergic inhibition, however, has not been well investigated. Here we addressed this issue using C56BL/6 mice. First, we confirmed previous observations that typical synaptic contacts were rare and confined to proximal axonal portions, with the remaining portions being mostly covered by astrocytic processes. Then we examined the expression of molecules involved in GABAergic signaling, including GABA synthetic enzyme glutamic acid decarboxylase (GAD), vesicular GABA transporter vesicular inhibitory amino acid transporter (VIAAT), cytomatrix active zone protein bassoon, GABA receptor GABA A R␣1, and cell adhesion molecule neuroligin-2. These molecules were recruited to form a functional assembly at perisomatic BC-PC synapses and along the AIS of hippocampal and neocortical pyramidal cells. GAD and VIAAT immunogold labeling was five times lower in the pinceau formation compared with perisomatic BC terminals and showed no accumulation toward the AIS. Moreover, bassoon, neuroligin-2, and GABA A R␣1 formed no detectable clusters along the ankyrin-G-positive AIS proper. These findings indicate that GABAergic signaling machinery is organized loosely and even incompletely in the pinceau formation. Together, BCs do not appear to exert GABAergic synaptic inhibition on the AIS, although the mode of action of the pinceau formation remains to be explored.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation

Iwakura

Uchigashima²,

Miyazaki³

et al. 2012

Journal of Neuroscience

View full text Add to dashboard Cite

show abstract

“…Our data indicate that, excepting a blockade of nodal excitability, which impedes propagation of high-frequency spikes, Purkinje cell firing is relatively resistant to modulation of Na channels beyond the initial segment. In contrast, perisomatic synaptic inhibition appears well situated to limit firing effectively (Palay and Chan-Palay, 1974;Bobik et al, 2004). Firing is also likely to be sensitive to modulation of perisomatic Na channels, e.g., by kinases and/or phosphatases (Cantrell and Catterall, 2001).…”

Section: Discussionmentioning

confidence: 99%

Relative Contributions of Axonal and Somatic Na Channels to Action Potential Initiation in Cerebellar Purkinje Neurons

2006

View full text Add to dashboard Cite

Neuronal excitability is likely to be regulated by the site of action potential initiation, the location on a neuron that crosses threshold first. Although initiation is axonal in many neurons, in Purkinje cells, somatic conductances can generate spontaneous action potentials, suggesting that the perisomatic region (soma and/or initial segment) contributes to spike initiation and may regulate firing. To identify directly the cellular regions at which Na channel modulation significantly influences firing, we measured spontaneous and evoked action potentials in Purkinje cells in cerebellar slices from postnatal day 14 -28 mice while applying drugs locally to either the soma/initial segment or the first node of Ranvier. Na currents were decreased by tetrodotoxin (TTX) or increased by ␤-pompilidotoxin (␤-PMTX). Dual somatic and axonal recordings indicated that spike thresholds and input-output curves were sensitive to TTX or ␤-PMTX at the perisomatic region but were unchanged by either drug at the first node. When perisomatic Na channel availability was reduced with subsaturating TTX, however, the input-output curve became shallower during additional TTX block of nodal channels, revealing a latent role for nodal Na channels in facilitating firing. In perisomatic TTX, axons failed to generate spontaneous or evoked spike trains. In contrast, choline block of the initial segment alone altered normal input-output curves. The data suggest that, although the first node reliably follows action potentials, spike initiation in Purkinje neurons occurs in the initial segment. Moreover, Purkinje cell output depends on the density, availability, and kinetics of perisomatic Na channels, a characteristic that may distinguish spontaneously firing from quiescent neurons.

show abstract

“…1), the projection neurons, Purkinje cells, express Kv3.3 throughout the cell and Kv3.4 largely in dendrites (Martina et al, 2003;McMahon et al, 2004;Chang et al, 2007). Granule cells express Kv3.1 and Kv3.3 (Weiser et al, 1995;Sekirnjak et al, 1997;Ozaita et al, 2002), whereas basket cells express Kv3.2 and Kv3.4 channel subunits in the pinceaux (Veh et al, 1995;Bobik et al, 2004). In the deep cerebellar nuclei (DCN) and analogous vestibular nuclei, mRNA for all subfamily members is present (Weiser et al, 1994), with Kv3.1 and Kv3.3 protein is expressed in large, presumably glutamatergic projection neurons (Weiser et al, 1995;McMahon et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels inKcnc3-Null Mice RequiresKcnc1

Hurlock¹,

Bose²,

Pierce³

et al. 2009

J. Neurosci.

View full text Add to dashboard Cite

The role of cerebellar Kv3.1 and Kv3.3 channels in motor coordination was examined with an emphasis on the deep cerebellar nuclei (DCN). Kv3 channel subunits encoded by Kcnc genes are distinguished by rapid activation and deactivation kinetics that support high-frequency, narrow action potential firing. Previously we reported that increased lateral deviation while ambulating and slips while traversing a narrow beam of ataxic Kcnc3-null mice were corrected by restoration of Kv3.3 channels specifically to Purkinje cells, whereas Kcnc3-mutant mice additionally lacking one Kcnc1 allele were partially rescued. Here, we report mice lacking all Kcnc1 and Kcnc3 alleles exhibit no such rescue. For Purkinje cell output to reach the rest of the brain it must be conveyed by neurons of the DCN or vestibular nuclei. As Kcnc1, but not Kcnc3, alleles are lost, mutant mice exhibit increasing gait ataxia accompanied by spike broadening and deceleration in DCN neurons, suggesting the facet of coordination rescued by Purkinje-cell-restricted Kv3.3 restoration in mice lacking just Kcnc3 is hypermetria, while gait ataxia emerges when additionally Kcnc1 alleles are lost. Thus, fast repolarization in Purkinje cells appears important for normal movement velocity, whereas DCN neurons are a prime candidate locus where fast repolarization is necessary for normal gait patterning.

show abstract

Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau

Cited by 35 publications

References 48 publications

Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation

Lack of Molecular-Anatomical Evidence for GABAergic Influence on Axon Initial Segment of Cerebellar Purkinje Cells by the Pinceau Formation

Relative Contributions of Axonal and Somatic Na Channels to Action Potential Initiation in Cerebellar Purkinje Neurons

Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels inKcnc3-Null Mice RequiresKcnc1

Contact Info

Product

Resources

About