The Journal of Neurophysiology Vol. 80 No. 1 July 1998, pp. 350-364
Copyright ©1998 The American Physiological Society

Increased Calcium Buffering in Basal Forebrain Neurons During Aging

David Murchison and William H. Griffith

Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University Health Science Center, College Station, Texas 77843-1114

Murchison, David and William H. Griffith. 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 ([Ca²⁺]_i), and time course of [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 [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.

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