Aging of cholinergic synapses in the avian iris. Part I--Biochemical studies

The present experiments were designed to test acetylcholine (ACh) release from cholinergic nerve endings of the chicken iris during aging. Either a one-step K+ stimulated release scheme or a more strenuous two-step depletion-reloading-release scheme were used. First, we found that independent of the scheme of release, as demonstrated by a lower peak release, slower time to peak and a lower rate of increase, the 3-year-old iris released less 3H-ACh than the 4-month-old iris. In order to analyze this effect of aging, we determined five basic parameters of ACh metabolism, including total acetylcholine (ACh) and choline (Ch) levels, 3H-ACh, 3H-Ch and 3H-phosphorylcholine (PhCh) formed from exogenous 3H-Ch, for each experimental type and for the two ages. There appear to be major differences in the handling of both the total Ch and newly labelled (3H-Ch) pools between the two ages. In addition, the homeostatic control system for Ch levels in the older tissue appears to be less efficient and incapable of handling strenuous release tests. This defect of the older tissue to preserve its Ch pool may, in part, be responsible for the drastic decrease in ACh levels seen in the older iris. Together with the demonstrated reduction in neurotransmitter level and in uptake of Ch, the reduction in release demonstrated here forms a characteristic triade of age-related defects which may have important implications for our understanding of aging processes in cholinergic terminals.