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.
|Number of pages
|Biochimica et Biophysica Acta - Molecular Basis of Disease
|Published - Apr 2012
Bibliographical noteFunding Information:
Work supported by NIH grants AG033649 to O.T.; AG004542 and AG010836 to P.W.L.; and AG027297 to C.M.N. The authors wish to thank Dr. Eric Blalock for important technical assistance.
- Alzheimer's disease
- Calcium dyshomeostasis
- Cognitive impairment
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology