Caffeine releasable stores of Ca2+ show depletion prior to the final steps in delayed CA1 neuronal death.
In addition to their role in signaling, Ca2+ ions in the endoplasmic reticulum also regulate important steps in protein processing and trafficking that are critical for normal cell function. Chronic depletion of Ca2+ in the endoplasmic reticulum has been shown to lead to cell degeneration and has been proposed as a mechanism underlying delayed neuronal death following ischemic insults to the CNS. Experiments here have assessed the relative content of ryanodine receptor-gated stores in CA1 neurons by measuring cytoplasmic Ca2+ increases induced by caffeine. These measurements were performed on CA1 neurons, in slice, from normal gerbils, and compared with responses from this same population of neurons 54-60 h after animals had undergone a standard ischemic insult: 5-min bilateral occlusion of the carotid arteries. The mean amplitude of responses in the postischemic population were less than one-third of those in control or sham-operated animals, and 35% of the neurons from postischemic animals showed very small responses that were approximately 10% of the control population mean. Refilling of these stores after caffeine challenges was also impaired in postischemic neurons. These observations are consistent with our earlier finding that voltage-gated influx is sharply reduced in postischemic in CA1 neurons and the hypothesis that the resulting depletion in endosomal Ca2+ is an important cause of delayed neuronal death.
Xing
Hong
H
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Azimi-Zonooz
Aryan
A
Shuttleworth
C William
CW
Connor
John A
JA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D017536:Carotid Artery, Common; D016923:Cell Death / Q000187:drug effects*; D023921:Coronary Stenosis; D016257:Fura-2 / Q000031:analogs & derivatives*; D005849:Gerbillinae; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000502:physiology
D019837:Ryanodine Receptor Calcium Release Channel; C049925:fura-2-am; D002110:Caffeine; D002118:Calcium; D016257:Fura-2