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 microM), 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'-tetraacetomethylester (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.
Tsai
H
H
Department of Pharmacology, College of Medicine, University of California, Irvine 92697, USA.
Hewitt
C W
CW
Buchholz
J N
JN
Duckles
S P
SP
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008928:Mitochondria / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000502:physiology; D013564:Sympathetic Nervous System / Q000254:growth & development / Q000378:metabolism*; D013623:Tail / Q000098:blood supply
D002614:Chelating Agents; D004140:Dinitrophenols; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D009638:Norepinephrine