title: Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease.
abstract: Increased function of neuronal L-type voltage-sensitive Ca(2+) channels (L-VSCCs) is strongly linked to impaired memory and altered hippocampal synaptic plasticity in aged rats. However, no studies have directly assessed L-VSCC function in any of the common mouse models of Alzheimer's disease where neurologic deficits are typically more robust. Here, we used cell-attached patch-clamp recording techniques to measure L-VSCC activity in CA1 pyramidal neurons of partially dissociated hippocampal "zipper" slices prepared from 14-month-old wild-type mice and memory-impaired APP/PS1 double knock-in mice. Surprisingly, the functional channel density of L-VSCCs was significantly reduced in the APP/PS1 group. No differences in voltage dependency and unitary conductance of L-VSCCs were observed. The results suggest that mechanisms for Ca(2+) dysregulation can differ substantially between animal models of normal aging and models of pathological aging.
authors.affiliation: Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. othibau@uky.edu
authors.forename: Olivier
authors.initials: O
authors.lastname: Thibault
authors.forename: Tristano
authors.initials: T
authors.lastname: Pancani
authors.forename: Philip W
authors.initials: PW
authors.lastname: Landfield
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Norris
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type