Thibault Olivier, Pancani Tristano, Landfield Philip W, Norris Christopher M
Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Biochim Biophys Acta. 2012 Apr;1822(4):546-9. doi: 10.1016/j.bbadis.2012.01.004. Epub 2012 Jan 10.
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.
神经元L型电压敏感性钙通道（L-VSCCs）功能增强与老年大鼠记忆受损和海马突触可塑性改变密切相关。然而，在任何常见的阿尔茨海默病小鼠模型中，均未直接评估L-VSCC功能，而在这些模型中神经功能缺损通常更为严重。在此，我们采用细胞贴附式膜片钳记录技术，测量了来自14月龄野生型小鼠和记忆受损的APP/PS1双敲入小鼠制备的部分解离海马“拉链”切片CA1锥体神经元中的L-VSCC活性。令人惊讶的是，APP/PS1组中L-VSCCs的功能通道密度显著降低。未观察到L-VSCCs在电压依赖性和单通道电导方面的差异。结果表明，正常衰老动物模型和病理性衰老模型之间Ca(2+)失调的机制可能存在显著差异。
