Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease

Increased function of neuronal L-type voltage-sensitive Ca2 + 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 Ca2 + dysregulation can differ substantially between animal models of normal aging and models of pathological aging.

► Increased activity of L-type Ca2 + channels is linked to cognitive decline with aging. ► L channel activity has not been assessed in mouse models of Alzheimer's disease (AD). ► L channel activity was investigated in hippocampal “zipper” slices from APP/PS1 mice. ► Surprisingly, APP/PS1 mice showed reduced L channel activity compared to wild types. ► Ca2 + dysregulation may be independent of L channels in some mouse models of AD.