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The Journal of Neuroscience, August 15, 2002, 22(16):7234-7243
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, and John F. Disterhoft Department of Physiology, Northwestern University, Chicago, Illinois 60611-3008
Aging is associated with learning deficits and a decrease in neuronal excitability, reflected by an enhanced post-burst afterhyperpolarization (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 (sIAHP), a major constituent of the AHP, also facilitate learning in aging animals, the sIAHP was pharmacologically isolated and characterized. Aging neurons were found to have an enhanced sIAHP, the amplitude of which was significantly correlated to the amplitude of the AHP (r = 0.63; p < 0.001). Thus, an enhanced sIAHP contributes to the enhanced AHP in aging. No differences were found in the membrane resistance, capacitance, or kinetic and voltage-dependent properties of the sIAHP. 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 sIAHP in the presence of an L-type Ca2+ channel blocker, nimodipine (10 µM). Nimodipine caused quantitatively greater reductions in the sIAHP in aging neurons than in young neurons; however, the residual sIAHP 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 sIAHP in aging is a mechanism that contributes to age-related learning deficits.
Key words: slow afterhyperpolarization; aging; L-type Ca2+ channels; whole-cell voltage clamp; current clamp; neuronal excitability; plasticity; nimodipine
* J.M.P. and W.W.W. contributed equally to this study.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22167234-10$05.00/0
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