Age-related enhancement of the slow outward calcium-activated potassium current in hippocampal CA1 pyramidal neurons in vitro

John M. Power, Wendy W. Wu, Evgeny Sametsky, M. Mathew Oh, John F. Disterhoft

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Aging is associated with learning deficits and a decrease in neuronal excitability, reflected by an enhanced post-burst afte-rhyperpolarization (AHP), in CA1 hippocampal pyramidal neurons. To identify the current(s) underlying the AHP altered in aging neurons, whole-cell voltage-clamp recording experiments were performed in hippocampal slices from young and aging rabbits. Similar to previous reports, aging neurons were found to rest at more hyperpolarized potentials and have larger AHPs than young neurons. Given that compounds that reduce the slow outward calcium-activated potassium current (S/AHP), a major constituent of the AHP, also facilitate learning in aging animals, the S/AHP was pharmacologically isolated and characterized. Aging neurons were found to have an enhanced S/AHP, the amplitude of which was significantly correlated to the amplitude of the AHP (r = 0.63; p < 0.001). Thus, an enhanced S/AHP contributes to the enhanced AHP in aging. No differences were found in the membrane resistance, capacitance, or kinetic and voltage-dependent properties of the S/AHP. Because enhanced AHP in aging neurons has been hypothesized to be secondary to an enhanced Ca2+ influx via the voltage-gated L-type Ca2+ channels, we further examined the S/AHP in the presence of an L-type Ca2+ channel blocker, nimodipine (10 μM). Nimodipine caused quantitatively greater reductions in the S/AHP in aging neurons than in young neurons; however, the residual S/AHP was still significantly larger in aging neurons than in young neurons. Our data, in conjunction with previous studies showing a correlation between the AHP and learning, suggest that the enhancement of the S/AHP in aging is a mechanism that contributes to age-related learning deficits.

Original languageEnglish (US)
Pages (from-to)7234-7243
Number of pages10
JournalJournal of Neuroscience
Volume22
Issue number16
DOIs
StatePublished - Aug 15 2002

Keywords

  • Aging
  • Current clamp
  • L-type Ca channels
  • Neuronal excitability
  • Nimodipine
  • Plasticity
  • Slow afterhyperpolarization
  • Whole-cell voltage clamp

ASJC Scopus subject areas

  • Neuroscience(all)

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