Developmental regulation of the A-type potassium-channel current in hippocampal neurons: Role of the Kvβ1.1 subunit

T. Falk, R. K. Kilani, L. A. Strazdas, R. S. Borders, J. V. Steidl, A. J. Yool, S. J. Sherman

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvβ1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA. Whole-cell patch clamp recordings of rat hippocampal pyramidal neurons in primary culture showed a developmental decrease in the time constant of inactivation (τin) of voltage-gated K+ currents: 17.9±1.5 ms in young neurons (5-7 days in vitro; n=53, mean±S.E.M.); 9.9±1.0 ms in mature neurons (12-15 days in vitro; n=72, mean±S.E.M., P<0.01). During the same developmental time, the level of Kvβ1.1 transcript increased more than two-fold in vitro and in vivo, determined by semi-quantitative reverse transcriptase-polymerase chain reaction for hippocampus. The hypothesis that up-regulation of Kvβ1.1 led to the changes in τin was tested in vitro, using antisense knockdown. Kvβ1.1-specific antisense DNA was introduced with a modified herpes virus co-expressing enhanced green fluorescent protein and knockdown of Kvβ1.1 was verified by immunocytochemistry. Following transduction with the antisense virus, mature neurons reverted to τin values characteristic of young neurons: 18.3±2.4 ms (n=20). The effect of antisense knockdown on electrical excitability was tested using current-clamp protocols to induce repetitive firing. Treatment with the antisense virus increased the interspike interval over a range of membrane depolarization (baseline membrane potential=-40 to +20 mV). This effect was most pronounced at -40 mV, where the ISI of the first pair of action potentials was nearly doubled. These data indicate that Kvβ1.1 contributes to the developmental control of IA in hippocampal neurons and that the magnitude of effect is sufficient to regulate electrical excitability. Viral-mediated antisense knockdown of Kvβ1.1 is capable of decreasing the electrical excitability of post-mitotic hippocampal neurons, suggesting this approach has applicability to gene therapy of neurological diseases associated with hyperexcitability.

Original languageEnglish (US)
Pages (from-to)387-404
Number of pages18
Issue number2
StatePublished - Aug 22 2003


  • Antisense DNA
  • Gene therapy
  • Herpes simplex virus 1
  • Voltage clamp

ASJC Scopus subject areas

  • General Neuroscience


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