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Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons.

Genes Kcna1 and Kcna2 code for the voltage-dependent potassium channel subunits Kv1.1 and Kv1.2, which are coexpressed in large axons and commonly present within the same tetramers. Both contribute to the low-voltage-activated potassium current I Kv1, which powerfully limits excitability and facilitates temporally precise transmission of information, e.g., in auditory neurons of the medial nucleus of the trapezoid body (MNTB). Kcna1-null mice lacking Kv1.1 exhibited seizure susceptibility and hyperexcitability in axons and MNTB neurons, which also had reduced I Kv1. To explore whether a lack of Kv1.2 would cause a similar phenotype, we created and characterized Kcna2-null mice (-/-). The -/- mice exhibited increased seizure susceptibility compared with their +/+ and +/- littermates, as early as P14. The mRNA for Kv1.1 and Kv1.2 increased strongly in +/+ brain stems between P7 and P14, suggesting the increasing importance of these subunits for limiting excitability. Surprisingly, MNTB neurons in brain stem slices from -/- and +/- mice were hypoexcitable despite their Kcna2 deficit, and voltage-clamped -/- MNTB neurons had enlarged I Kv1. This contrasts strikingly with the Kcna1-null MNTB phenotype. Toxin block experiments on MNTB neurons suggested Kv1.2 was present in every +/+ Kv1 channel, about 60% of +/- Kv1 channels, and no -/- Kv1 channels. Kv1 channels lacking Kv1.2 activated at abnormally negative potentials, which may explain why MNTB neurons with larger proportions of such channels had larger I Kv1. If channel voltage dependence is determined by how many Kv1.2 subunits each contains, neurons might be able to fine-tune their excitability by adjusting the Kv1.1:Kv1.2 balance rather than altering Kv1 channel density.

Pubmed ID: 17634333


  • Brew HM
  • Gittelman JX
  • Silverstein RS
  • Hanks TD
  • Demas VP
  • Robinson LC
  • Robbins CA
  • McKee-Johnson J
  • Chiu SY
  • Messing A
  • Tempel BL


Journal of neurophysiology

Publication Data

September 11, 2007

Associated Grants

  • Agency: NIDCD NIH HHS, Id: DC-003805
  • Agency: NIDCD NIH HHS, Id: DC-02739
  • Agency: NIDCD NIH HHS, Id: P30-DC-04661
  • Agency: NIDCD NIH HHS, Id: T32-DC-05361
  • Agency: NIGMS NIH HHS, Id: T32-GM-07108

Mesh Terms

  • Aging
  • Animals
  • Brain Stem
  • Genetic Vectors
  • Genome
  • Genotype
  • Kv1.2 Potassium Channel
  • Life Expectancy
  • Mice
  • Mice, Knockout
  • Neurons
  • Open Reading Frames
  • Restriction Mapping
  • Seizures
  • Shaker Superfamily of Potassium Channels