Episodic Ataxia Type 1 Mutations in the Human Kv1.1 Potassium Channel Alter hKvβ1-Induced N-Type Inactivation

Brooke Maylie, Erinne Bissonnette, Michael Virk, John P. Adelman, James G. Maylie

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder affecting both central and peripheral nerve function, causing attacks of imbalance and uncontrolled movements. Genetic linkage studies have identified mutations in the gene encoding the voltage-gated delayed rectifier potassium channel Kv1.1 as underlying EA1. The EA1 mutations E325D and V408A, residing near the cytoplasmic ends of S5 and S6, respectively, induce an unstable open state, resulting in an ∼10-fold increase in deactivation rates compared with wild-type (WT) channels. Coexpression of EA1 mutations with human Kvβ1 (hKvβ1) subunits in Xenopus oocytes yielded channels with altered rapid N-type inactivation. Compared with WT channels, inactivation was approximately twofold slower for homomeric E325D or V408A channels and 1.5-fold slower for heteromeric channels composed of two WT and two E325D or V408A subunits. Recovery from inactivation was ∼10-fold faster for homomeric E325D or V408A channels and threefold to fourfold faster for heteromeric WT and E325D or V408A channels compared with WT channels. Currents during successive pulses 3 msec in duration given at a rate of 40 kHz decayed e-fold in approximately four pulses for homomeric E325D or V408A and ∼2.5 pulses for heteromeric channels compared with approximately one pulse for WT channels. These results show that channels containing E325D or V408A subunits, which destabilize the open state, increase the rate of recovery from inactivation. The slower onset and more rapid recovery of hKvβ1-induced inactivation in channels containing these EA1 subunits may affect temporal integration of action potential firing rates.

Original languageEnglish (US)
Pages (from-to)4786-4793
Number of pages8
JournalJournal of Neuroscience
Issue number12
StatePublished - Jun 15 2002


  • Episodic ataxia type 1
  • Inactivation
  • Kv1.1
  • Kvβ1
  • Potassium channel
  • Recovery from inactivation

ASJC Scopus subject areas

  • Neuroscience(all)


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