title: Adrenergic nerves compensate for a decline in calcium buffering during ageing.
abstract: 1. The ubiquitous involvement of intracellular calcium ([Ca2+]i) in multiple neuronal pathways has led investigators to suggest that dysfunction of calcium homeostasis may be the primary mediator of age-related neuronal degeneration. Recently, it was shown that sympathetic neurones from superior cervical ganglion (SCG) of aged rats demonstrate decreased sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA) function and that aged neurones are more dependent upon mitochondria to control K+-evoked [Ca2+]i transients. 2. Therefore, in the present study we investigated age-related changes in ATP-dependent calcium pumps of plasma membrane Ca2+-ATPase (PMCA) and SERCA in acutely dissociated SCG cells from Fischer-344 rats aged 6 and 20 months. To distinguish between PMCA and SERCA pump activity, we applied the Ca2+-ATPase blocker vanadate and measured rates of recovery of K+-evoked [Ca2+]i transients by fura-2 microfluorometry. 3. Young SCG cells showed a biphasic response to vanadate over the vanadate concentration range (0.01-100 microM); however, old SCG cells showed only a single response over the same concentration range. Additionally, old SCG cells showed a greater sensitivity to Ca2+-ATPase blockade by vanadate. 4. The contribution of mitochondrial calcium uptake to regulate [Ca2+]i was also investigated. To measure the impact of mitochondrial calcium uptake, PMCAs and SERCAs were blocked with vanadate (100 microM) and extracellular sodium was replaced with tetraethylammonium (TEA) to block Na+/Ca2+-exchange. Treated SCG cells showed a decline of 50% in rate of recovery of [Ca2+]i in both 6- and 20-month-old cells; however, this effect did not vary with age. 5. These data suggest that there is an age-related decline in function of SERCAs, with an increased reliance on PMCAs to control high K+-evoked [Ca2+]i transients. In addition, there appears to be no age-related change in the capacity of the mitochondria to restore [Ca2+]i transients to basal levels.
authors.affiliation: Department of Pharmacology, Loma Linda University School of Medicine, CA 92350, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Pottorf
authors.forename: S P
authors.initials: SP
authors.lastname: Duckles
authors.forename: J N
authors.initials: JN
authors.lastname: Buchholz
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002138:Calibration; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
chemical_list: D002021:Buffers; D004791:Enzyme Inhibitors; D014638:Vanadates; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium