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: Olivier Thibault, Tristano Pancani, Philip W Landfield, Christopher M Norris
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1822 Issue 4 Pg. 546-9 (Apr 2012) ISSN: 0006-3002 [Print] Netherlands
• PMID: 22265986 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Calcium Channels, L-Type

Topics

• Alzheimer Disease (physiopathology)
• Animals
• Calcium Channels, L-Type (physiology)
• Disease Models, Animal
• Male
• Mice
• Mice, Transgenic
• Neurons (physiology)