title: Reduced mitochondrial buffering of voltage-gated calcium influx in aged rat basal forebrain neurons.
abstract: Alterations of neuronal Ca(2+) homeostatic mechanisms could be responsible for many of the cognitive deficits associated with aging in mammals. Mitochondrial participation in Ca(2+) signaling is now recognized as a prominent feature in neuronal physiology. We combined voltage-clamp electrophysiology with Ca(2+)-sensitive ratiometric microfluorimetry and laser scanning confocal microscopy to investigate the participation in Ca(2+) buffering of in situ mitochondria in acutely dissociated basal forebrain neurons from young and aged F344 rats. By pharmacologically blocking mitochondrial Ca(2+) uptake, we determined that mitochondria were not involved in rapid buffering of small Ca(2+) influx through voltage-gated Ca(2+) channels (VGCCs) in the somatic compartment. For larger Ca(2+) influx, aged mitochondria showed a significant buffering deficit. Evidence obtained with the potentiometric indicator, JC-1, suggests a significantly reduced mitochondrial membrane potential in aged neurons. These results support the interpretation that there is a fundamental difference in the way young and aged neurons buffer Ca(2+), and a corresponding difference in the quality of the Ca(2+) signal experienced by young and aged neurons for different intensities of cytoplasmic Ca(2+) influx.
authors.affiliation: Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
authors.forename: David
authors.initials: D
authors.lastname: Murchison
authors.forename: David C
authors.initials: DC
authors.lastname: Zawieja
authors.forename: William H
authors.initials: WH
authors.lastname: Griffith
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002021:Buffers; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002021:Buffers; D015220:Calcium Channels; D002110:Caffeine; D011188:Potassium; D002118:Calcium