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Schematic drawing of the conventional membrane topology of a human Kv1.1 subunit. Four such subunits comprise a functional homotetrameric channel. Different subunits belonging to the Kv1 subfamily may form heterotetrameric channels. The positions of pathogenic variants identified to date in individuals with EA1 are indicated.
Modified from D'Adamo et al [2012]; used by permission of Nova Science Publishers, Inc.

Worldwide distribution of SCA subtypes[Schöls et al 1997, Moseley et al 1998, Saleem et al 2000, Storey et al 2000, Tang et al 2000, Maruyama et al 2002, Silveira et al 2002, van de Warrenburg et al 2002, Dryer et al 2003, Brusco et al 2004, Schöls et al 2004, Shimizu et al 2004, Zortea et al 2004, Jiang et al 2005, Jiang et al 2013]
Note: The data in Figure 1 was gathered before the use of multigene panels and exome/genome sequencing. The data are still appropriate for nucleotide repeat disorders; new SCAs found by exome/genome sequencing represent a very small percentage. There have been no recent regional updates to SCA subtype distribution in Australia or sub-Saharan Africa.
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Figure published courtesy of L Schöls, P Bauer, T Schmidt, T Schulte, O Reiss of University of Tübingen and Ruhr-University Bochum, Germany

Proposed effects of EA1-causing pathogenic variants on basket cell and Purkinje cell inhibitory outputs
The diagram shows a basket cell that has synapses on the initial segment and soma of a number of Purkinje cells from the cerebellar cortex of an unaffected individual (left) compared to an individual with EA1 (right). The reduced delayed rectifier function of EA1 heteromeric channels comprising Kv1.1 and Kv1.2 subunits, which are expressed at the presynaptic level of basket cells, may increase the membrane excitability, prolong their action potential duration, and enhance Ca²⁺ ion influx. Larger amounts of γ-aminobutyric acid (GABA) may be released from basket cell terminals reducing the inhibitory outputs of the relevant Purkinje cells. As a result, the output of the entire cerebellum to the rest of the brain may be markedly altered leading to the cerebellar symptoms characteristic of EA1 (see D'Adamo et al 1999, Figure 7).
Reused by permission of FASEB Journal