Murchison D, Griffith W H
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843-1114, USA.
J Neurophysiol. 1998 Jul;80(1):350-64. doi: 10.1152/jn.1998.80.1.350.
Increased calcium buffering in basal forebrain neurons during aging. J. Neurophysiol. 80: 350-364, 1998. Alterations of neuronal calcium (Ca2+) homeostasis are thought to underlie many age-related changes in the nervous system. Basal forebrain neurons are susceptible to changes associated with aging and to related dysfunctions such as Alzheimer's disease. It recently was shown that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of aged (24-27 mo) F344 rats have an increased current influx through voltage-gated Ca2+ channels (VGCCs) relative to those of young (1-4. 5 mo) rats. Possible age-related changes in Ca2+ buffering in these neurons have been investigated using conventional whole cell and perforated-patch voltage clamp combined with fura-2 microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i), Ca2+ influx, Ca2+ transients (Delta[Ca2+]i), and time course of Delta[Ca2+]i were quantitated, and rapid Ca2+ buffering values were calculated in MS/nDB neurons from young and aged rats. The involvement of the smooth endoplasmic reticulum (SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related increase in rapid Ca2+ buffering and Delta[Ca2+]i time course was observed, although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible buffering mechanisms were found to have roles in Ca2+ buffering, but they did not mediate the age-related changes. These findings suggest a model in which some aging central neurons could compensate for increased Ca2+ influx with greater Ca2+ buffering.
衰老过程中基底前脑神经元钙缓冲能力增强。《神经生理学杂志》80: 350 - 364, 1998年。神经元钙（Ca2+）稳态的改变被认为是神经系统中许多与年龄相关变化的基础。基底前脑神经元易受与衰老相关的变化以及诸如阿尔茨海默病等相关功能障碍的影响。最近研究表明，与年轻（1 - 4.5月龄）F344大鼠相比，老年（24 - 27月龄）大鼠内侧隔核和斜角带核（MS/nDB）的神经元通过电压门控Ca2+通道（VGCCs）的电流内流增加。利用传统的全细胞和穿孔膜片电压钳结合fura - 2微荧光技术研究了这些神经元中可能与年龄相关的Ca2+缓冲变化。对基础细胞内Ca2+浓度（[Ca2+]i）、Ca2+内流、Ca2+瞬变（Δ[Ca2+]i）以及Δ[Ca2+]i的时间进程进行了定量，并计算了年轻和老年大鼠MS/nDB神经元的快速Ca2+缓冲值。用内质网（SER）Ca2+摄取阻滞剂毒胡萝卜素研究了内质网的参与情况。尽管基础[Ca2+]i不随年龄变化，但观察到快速Ca2+缓冲和Δ[Ca2+]i时间进程随年龄增加。发现SER和内源性可扩散缓冲机制在Ca2+缓冲中起作用，但它们并未介导与年龄相关的变化。这些发现提示了一个模型，即一些衰老的中枢神经元可以通过更大的Ca2+缓冲来补偿增加的Ca2+内流。
