Intracellular calcium buffering declines in aging adrenergic nerves

Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves increased with advancing age in the Fischer-344 rat when function of norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were blocked. When calcium channels were bypassed with the ionophore, ionomycin (4 μM), norepinephrine release from aged nerves (20 months) was still elevated as compared to 6-month-old nerves. Norepinephrine release stimulated by high K⁺ was also higher in 20-month nerves. The intracellular calcium chelator, 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'- tetraaceto-methylester (BAPTA/AM), was used to determine whether age-related increases in norepinephrine release could be reversed with the addition of an artificial intracellular calcium buffer. Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both old and young tail arteries; however, the effect was significantly greater in older arteries. When mitochondrial calcium uptake was compromised using the uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused a further decrease in stimulation-evoked norepinephrine release in 20-month tail arteries with much less effect in 6-month-old nerves. These results suggest that intracellular calcium buffering is less efficient in older nerves.