Kv3 voltage‐gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals

Brooke, Ruth E.; Moores, Thomas; Morris, Neil P.; Parson, Simon H.; Deuchars, Jim

doi:10.1111/j.1460-9568.2004.03730.x

Cited by 45 publications

(42 citation statements)

References 53 publications

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“…Furthermore, Kv3.3 antibody failed to stain in preabsorbtion controls, and the pattern of anti-Kv3.3 antibody staining overlapped with mRNA expression profiles in cerebellum and hippocampus (Brooke et al, 2004). Identical staining profiles were also observed for a different antiKv3.3 antibody and the anti-Kv3.3 antibody obtained from Alomone Labs used in the present study, suggesting that the two antibodies specifically recognize the correct antigen (Brooke et al, 2004). Anti-TWIK-1 polyclonal antibody (generous gift of Dr. Florian Lesage; Universite de Nice Sophia Antipolis, Valbonne, France) is a specific and extensively characterized (Lesage et al, 1996b;Cluzeaud et al, 1998;Lesage et al, 1997).…”

Section: Antibodiesmentioning

confidence: 63%

“…Western blots have shown that the antibody recognizes two bands that represent the glycosylated monomers ($110 kDa) and dimers ($220 kDa) for the antigen and when tested on Kv3.3 knock-out tissue anti-Kv3.3 antibody staining was negative (McMahon et al, 2004). Furthermore, Kv3.3 antibody failed to stain in preabsorbtion controls, and the pattern of anti-Kv3.3 antibody staining overlapped with mRNA expression profiles in cerebellum and hippocampus (Brooke et al, 2004). Identical staining profiles were also observed for a different antiKv3.3 antibody and the anti-Kv3.3 antibody obtained from Alomone Labs used in the present study, suggesting that the two antibodies specifically recognize the correct antigen (Brooke et al, 2004).…”

Section: Antibodiesmentioning

confidence: 77%

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Voltage-gated and two-pore-domain potassium channels in murine spiral ganglion neurons

Chen

Davis

2006

Hearing Research

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Section: Antibodiesmentioning

confidence: 63%

Section: Antibodiesmentioning

confidence: 77%

Voltage-gated and two-pore-domain potassium channels in murine spiral ganglion neurons

Chen

Davis

2006

Hearing Research

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“…Because Kv3.3 subunits are coexpressed with Kv3.4 in axon terminals of motor neurons at the neuromuscular junction in which the absence of Kv3.3 may affect neurotransmitter release (Brooke et al, 2004), we determined whether changes in muscle strength might have contributed to the observed motor phenotype. We placed individual mice on an inverted cage top and measured the latency to fall (maximal time, 180 s).…”

Section: Purkinje-cell-restricted Kv33 Reexpression Rescues Motor Fumentioning

confidence: 99%

Purkinje-Cell-Restricted Restoration of Kv3.3 Function Restores Complex Spikes and Rescues Motor Coordination inKcnc3Mutants

Hurlock

McMahon²,

Joho³

2008

J. Neurosci.

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The fast-activating/deactivating voltage-gated potassium channel Kv3.3 (Kcnc3) is expressed in various neuronal cell types involved in motor function, including cerebellar Purkinje cells. Spinocerebellar ataxia type 13 (SCA13) patients carrying dominant-negative mutations in Kcnc3 and Kcnc3-null mutant mice both display motor incoordination, suggested in mice by increased lateral deviation while ambulating and slips on a narrow beam. Motor skill learning, however, is spared. Mice lacking Kcnc3 also exhibit muscle twitches. In addition to broadened spikes, recordings of Kcnc3-null Purkinje cells revealed fewer spikelets in complex spikes and a lower intraburst frequency. Targeted reexpression of Kv3.3 channels exclusively in Purkinje cells in Kcnc3-null mice as well as in mice also heterozygous for Kv3.1 sufficed to restore simple spike brevity along with normal complex spikes and to rescue specifically coordination. Therefore, spike parameters requiring Kv3.3 function in Purkinje cells are involved in the ataxic null phenotype and motor coordination, but not motor learning.Key words: K channels; burst firing; motor dysfunction; cerebellum; Purkinje cell; complex spike IntroductionVoltage-gated potassium (Kv) channels of the Kv3 subfamily enable neurons to fire narrow action potentials at high frequencies beyond ϳ200 Hz. Four separate genes (Kcnc1-Kcnc4 ) encoding subunits Kv3.1-Kv3.4 are expressed in various combinations in CNS neurons in which they assemble into homotetrameric and heterotetrameric channels. Mice lacking the Kcnc3-encoded Kv3.3 subunit exhibit motor deficits manifested as increased lateral deviation while ambulating and increased slips while traversing a narrow beam (McMahon et al., 2004;Joho et al., 2006b). A role for Kv3.3 channels in motor coordination is also underscored by the recent finding that dominant-negative mutations found in the human KCNC3 gene correlate with the neurological disorder spinocerebellar ataxia 13 (Waters et al., 2006). Kv3-type channels are distinguished by exceptionally rapid kinetics of activation and deactivation, rendering them ideally suited to drive repolarization that is rapid, both in its onset and relief, so that the next action potential upstroke can occur with minimal delay in the absence of lingering afterhyperpolarization. High-frequency spiking is facilitated by both minimizing sodium channel inactivation through brief action potentials and by promoting sodium channel deinactivation through the excursion to negative potentials during the fast afterhyperpolarization. Indeed, the loss of Kv3-type channels results in broadened spikes accompanied by decelerated firing (Rudy and McBain, 2001). Unlike most other neuron types in which Kv3.3 subunits are expressed with other Kv3-type subunits, Purkinje cells express high levels of Kv3.3 and lower levels of Kv3.4 (Weiser et al., 1994;Martina et al., 2003). Loss of Kv3.3 results in a doubling of action potential duration (McMahon et al., 2004). Furthermore, blockade with tetraethylammonium (TEA) or BDS-I at a conc...

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“…There are four Kv3 isoforms, Kv3.1, Kv3.2,Kv3.3,and Kv3.4. Whereas Kv3.1,Kv3.2 and Kv3.4 are targeted to the nerve terminals of central neurons to regulate action potential duration and transmitter release (Rettig et al, 1992;Weiser et al, 1994;Ishikawa et al, 2003;Lien and Jonas, 2003;Matsukawa et al, 2003;Brooke et al, 2004;Goldberg et al, 2005), Kv3.3 and Kv3.4 are localized in the somatodendritic regions of cerebellar Purkinje cells to shape the large depolarization events (Martina et al, 2003). Each Kv3 isoform gives rise to multiple products by alternative splicing, which exclusively occurs at the C-terminal region.…”

Section: Introductionmentioning

confidence: 99%

The Axon–Dendrite Targeting of Kv3 (Shaw) Channels Is Determined by a Targeting Motif That Associates with the T1 Domain and Ankyrin G

Xu¹,

Cao²,

Xiao³

et al. 2007

J. Neurosci.

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Kv3 (Shaw) channels regulate rapid spiking, transmitter release and dendritic integration of many central neurons. Crucial to functional diversity are the complex targeting patterns of channel proteins. However, the targeting mechanisms are not known. Here we report that the axon-dendrite targeting of Kv3.1 is controlled by a conditional interaction of a C-terminal axonal targeting motif (ATM) with the N-terminal T1 domain and adaptor protein ankyrin G. In cultured hippocampal neurons, although the two splice variants of Kv3.1, Kv3.1a and Kv3.1b, are differentially targeted to the somatodendritic and axonal membrane, respectively, the lysine-rich ATM is surprisingly common for both splice variants. The ATM not only directly binds to the T1 domain in a Zn 2ϩ -dependent manner, but also associates with the ankyrin-repeat domain of ankyrin G. However, the full-length channel proteins of Kv3.1b display stronger association to ankyrin G than those of Kv3.1a, suggesting that the unique splice domain at Kv3.1b C terminus influences ATM binding to T1 and ankyrin G. Because ankyrin G mainly resides at the axon initial segment, we propose that it may function as a barrier for axon-dendrite targeting of Kv3.1 channels. In support of this idea, disrupting ankyrin G function either by over-expressing a dominant-negative mutant or by siRNA knockdown decreases polarized axon-dendrite targeting of both Kv3.1a and Kv3.1b. We conclude that the conditional ATM masked by the T1 domain in Kv3.1a is exposed by the splice domain in Kv3.1b, and is subsequently recognized by ankyrin G to target Kv3.1b into the axon.

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Kv3 voltage‐gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals

Cited by 45 publications

References 53 publications

Voltage-gated and two-pore-domain potassium channels in murine spiral ganglion neurons

Voltage-gated and two-pore-domain potassium channels in murine spiral ganglion neurons

Purkinje-Cell-Restricted Restoration of Kv3.3 Function Restores Complex Spikes and Rescues Motor Coordination inKcnc3Mutants

The Axon–Dendrite Targeting of Kv3 (Shaw) Channels Is Determined by a Targeting Motif That Associates with the T1 Domain and Ankyrin G

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