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This Article Full Text Full Text (PDF) All Versions of this Article: 92/5/2960    most recent 00015.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Xing, H. Articles by Connor, J. A. Search for Related Content PubMed PubMed Citation Articles by Xing, H. Articles by Connor, J. A.

Caffeine Releasable Stores of Ca²⁺ Show Depletion Prior to the Final Steps in Delayed CA1 Neuronal Death

¹Department of Neurosciences and ²Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131; and ³Department of Oral Surgery, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610

Submitted 6 January 2004; accepted in final form 15 June 2004

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 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.