title: Muscle-specific decrease in presynaptic calcium dependence and clearance during neuromuscular transmission in aged rats.
abstract: 1. Calcium regulation in the vicinity of synaptic release sites was measured indirectly at the neuromuscular junction of diaphragm, soleus, and extensor digitorum longus (EDL) muscles of rats 10 (mature adult) and 25-27 mo of age. 2. The rate of miniature end-plate potentials (MEPPs) per nerve terminal increased by 79% with age in EDL but did not change significantly in diaphragm or soleus; since MEPP rate depends, in part, on resting steady-state intracellular Ca2+ levels, ([Ca2+]i), it was inferred that these levels may be elevated by at least 16% in the aged EDL tissue. 3. The double-logarithmic relationship between extracellular Ca2+ ([Ca2+]e), and quantal release (m) was determined for [Ca2+]e between 0.5 and 1.2 mM. The slope (n) of this relationship was 4.1 and 3.2 in EDL muscles from the younger and the older animals, respectively; this difference was significant statistically. 4. A static model of the saturable cooperative relationship between [Ca2+]e and m was used to evaluate possible causes of the age-related change in this relationship. Changes resembling those seen in EDL during aging could be produced by relatively slight variations in the amount of Ca2+ entering the cell, intracellular buffering capacity, and several other related aspects of Ca2+ availability. The observed changes could not, however, be attributed quantitatively to increased steady-state [Ca2+]i. 5. The decay rates of synaptic facilitation and of posttetanic augmentation were prolonged by 164 and 227%, respectively, in EDL during aging. Since both of these phenomena have been attributed to residual Ca2+, it was inferred that rates of Ca2+ clearance from synaptic release sites were correspondingly slower in aged EDL. 6. Each of these age-associated changes in Ca2+ regulation was observed only in EDL and not in diaphragm or soleus. This specificity may be related to progressive disuse of EDL (a fast-twitch leg muscle), and consequently decreased expression of Ca2+-regulatory enzymes, during aging.
authors.affiliation: Department of Physiology, University of Wisconsin, Madison 53706.
authors.forename: D O
authors.initials: DO
authors.lastname: Smith
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D008959:Models, Neurological; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D011930:Reaction Time; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D002118:Calcium