Enhancement of GABA-activated membrane currents in aged Fischer 344 rat basal forebrain neurons.
Changes in GABAergic systems have been widely documented during development. Similar changes might also occur during aging, but little information is currently available. Whole-cell and single-channel GABAA-activated currents were studied in acutely dissociated basal forebrain neurons. An age-related increase in whole-cell GABA currents was observed in cells from aged (19-25 month) Fischer 344 rats. The GABA current from aged animals displayed a greater maximum response, with no change in EC50 or slope of the GABA response curve. A reduction in use-dependent slow receptor desensitization was also observed in aged cells. Single-channel conductance and channel open time were unchanged with age, suggesting no alteration in the properties of single GABA channels. The benzodiazepine, midazolam, potentiated GABA currents to a greater degree in aged animals, consistent with previous reports of enhanced benzodiazepine activity with age. Ontogeny of the GABAA receptor/ion channel complex may continue through the stages of development, maturation, and aging.
Griffith
W H
WH
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University, College Station 77843.
Murchison
D A
DA
D000200:Action Potentials / Q000187:drug effects; D000375:Aging / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004357:Drug Synergism; D015640:Ion Channel Gating / Q000187:drug effects; D007811:Lanthanum / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012688:Septum Pellucidum / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D007811:Lanthanum; D010424:Pentobarbital; D015032:Zinc; D008874:Midazolam; D001640:Bicuculline