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Intracellular calcium buffering declines in aging adrenergic nerves
H Tsai1, C W Hewitt, J N Buchholz
1Department of Pharmacology, College of Medicine, University of California, Irvine 92697, USA.
Neurobiology of Aging
|March 1, 1997
Summary
Aging impairs norepinephrine release regulation in rat tail arteries. Older nerves show less efficient intracellular calcium buffering, leading to elevated norepinephrine release.
Area of Science:
- Neuroscience
- Gerontology
- Pharmacology
Background:
- Advancing age is associated with altered neurotransmitter release.
- Norepinephrine (NE) release is critical for vascular function.
- Age-related changes in calcium handling may affect NE release.
Purpose of the Study:
- To investigate age-related alterations in norepinephrine release from rat tail artery adrenergic nerves.
- To determine the role of intracellular calcium buffering in age-dependent NE release.
Main Methods:
- Stimulation-evoked NE release was measured in tail arteries from young (6-month) and aged (20-month) Fischer-344 rats.
- Norepinephrine uptake and alpha-2 adrenoceptor function were blocked.
- Calcium channels were bypassed using ionomycin.
- Intracellular calcium buffering was assessed using BAPTA/AM.
- Mitochondrial calcium uptake was inhibited with dinitrophenol.
Main Results:
- Aging increased stimulation-evoked NE release, even when calcium channels were bypassed.
- BAPTA/AM significantly reduced NE release in both age groups, with a greater effect in aged arteries.
- Inhibition of mitochondrial calcium uptake exacerbated the effect of BAPTA/AM in aged nerves.
Conclusions:
- Intracellular calcium buffering mechanisms are less efficient in aged rat tail artery nerves.
- Impaired calcium buffering contributes to age-related increases in norepinephrine release.