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Abstract
Spinocerebellar ataxia 13 (SCA13), initially described in a four-generation French family, has now also been characterized in a large Filipino pedigree. Ongoing investigations continue to identify additional SCA13 families and individuals. Recently, studies have shown that mutations in the voltage-gated potassium channel KCNC3 are causative for SCA13. Sequence analysis of KCNC3 revealed mutations 1554G-->A (R420H) in the Filipino and 1639C-->A (F448L) in the French pedigrees. Both mutations alter KCNC3 function in a Xenopus laevis oocyte expression system. KCNC3(R420H), located in the voltage sensor of the channel, has no detectable channel activity when expressed alone, and strong dominant negative effects when coexpressed with wild-type KCNC3. KCNC3(F448L) shifts the activation curve in the negative direction and causes an approximately sevenfold slowing of channel closure. These mutations are expected to change the output characteristics of fast-spiking cerebellar neurons, where KCNC channels confer capacity for high-frequency repetitive firing.
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996, Pubmed,
Xenbase
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Brooke,
Immunohistochemical localisation of the voltage gated potassium ion channel subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord.
2006,
Pubmed
Duprat,
Susceptibility of cloned K+ channels to reactive oxygen species.
1995,
Pubmed
,
Xenbase
Goldman-Wohl,
Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei.
1994,
Pubmed
Gutman,
International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels.
2003,
Pubmed
Herman-Bert,
Mapping of spinocerebellar ataxia 13 to chromosome 19q13.3-q13.4 in a family with autosomal dominant cerebellar ataxia and mental retardation.
2000,
Pubmed
Martina,
Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons.
2003,
Pubmed
Matsukawa,
Motor dysfunction and altered synaptic transmission at the parallel fiber-Purkinje cell synapse in mice lacking potassium channels Kv3.1 and Kv3.3.
2003,
Pubmed
McKay,
Physiological and morphological development of the rat cerebellar Purkinje cell.
2005,
Pubmed
McKay,
Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells.
2004,
Pubmed
McMahon,
Allele-dependent changes of olivocerebellar circuit properties in the absence of the voltage-gated potassium channels Kv3.1 and Kv3.3.
2004,
Pubmed
Rudy,
Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing.
2001,
Pubmed
Ruppersberg,
Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.
1991,
Pubmed
,
Xenbase
Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Shieh,
Role of transmembrane segment S5 on gating of voltage-dependent K+ channels.
1997,
Pubmed
,
Xenbase
Smith-Maxwell,
Uncharged S4 residues and cooperativity in voltage-dependent potassium channel activation.
1998,
Pubmed
,
Xenbase
Vega-Saenz de Miera,
Modulation of K+ channels by hydrogen peroxide.
1992,
Pubmed
,
Xenbase
Waters,
An autosomal dominant ataxia maps to 19q13: Allelic heterogeneity of SCA13 or novel locus?
2005,
Pubmed
Waters,
Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes.
2006,
Pubmed
,
Xenbase
Weiser,
Differential expression of Shaw-related K+ channels in the rat central nervous system.
1994,
Pubmed
,
Xenbase
Yellen,
The voltage-gated potassium channels and their relatives.
2002,
Pubmed
