Episodic ataxia/myokymia mutations functionally expressed in the Shaker potassium channel

L. M. Boland, D. L. Price, K. A. Jackson

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Episodic ataxia type 1 is a rare, autosomal dominant neurological disorder caused by missense mutations of the Kv1.1 gene from the Shaker K+ channel subfamily. To study the functional effects of the disease-causing mutations in a robust K+ channel background, we introduced seven different episodic ataxia type 1 substitutions into the corresponding, conserved residues of the Shaker K+ channel. K+ channel currents expressed in Xenopus oocytes were studied by electrophysiology. All episodic ataxia type 1 mutations produced functional K+ channels. In a Shaker N-terminal deletion mutant with fast inactivation removed, current amplitudes were significantly reduced in channels harboring an episodic ataxia type 1 mutation. Six of the seven mutations also showed depolarizing shifts (+9 to +36 mV) in the conductance voltage dependence. One mutation (F307I) shifted the midpoint of the conductance-voltage relationship by 23 mV in the hyperpolarizing direction. Episodic ataxia type 1 mutations were also expressed in ShakerH4 with intact N-terminal inactivation. In this construct, current amplitudes for episodic ataxia type 1 mutants were not significantly different from wild-type channels. All mutations altered the voltage range of steady-state inactivation; most changes were coupled to the changes in activation gating. Some episodic ataxia type 1 mutants also caused significant changes in the kinetics of N-type (F307I, E395D) or C-type (F307I, E395D, V478A) inactivation. These results suggest that episodic ataxia type I mutations may change K+ channel function by two mechanisms: (i) reduced channel expression and (ii) altered channel gating.

Original languageEnglish (US)
Pages (from-to)1557-1564
Number of pages8
Issue number4
StatePublished - Jul 1999
Externally publishedYes


  • Activation
  • Episodic ataxia type 1
  • Inactivation
  • K channel
  • Voltage clamp

ASJC Scopus subject areas

  • General Neuroscience


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