Involvement of adenosine in ischemic and postischemic calcium regulation.
In the CA1 region of the hippocampus, ischemia or high-frequency stimulation of the glutamatergic input induces neuronal calcium uptake that is reflected as a decrease of the extracellular concentration of calcium ([Ca2+]ec. In this study, the effects of theophylline on these [Ca2+]ec shifts were examined in doses (20 mg/kg iv) where theophylline is mainly acting by blocking adenosine receptors. By using calcium-sensitive microelectrodes, [Ca2+]ec was concomitantly recorded in stratum pyramidale (SP) and stratum radiatum (SR) of the CA1 in adult Wistar rats, before, during, and for 6 h after transient forebrain ischemia. During ischemia (4-vessel occlusion, 20 min), the [Ca2+]ec decrease in SR preceded (by 11 +/- 4 s; mean +/- SEM) the [Ca2+]ec decrease in SP. Administration of theophylline prior to ischemia reduced the time from vessel-occlusion to the ischemic decrease in [Ca2+]ec (from 3.0 +/- 0.3 to 0.9 +/- 0.1 min; mean +/- SEM; p < 0.01). During electrically evoked burst firing, the [Ca2+]ec shift was augmented by theophylline in nonischemic controls (by 29 +/- 4%; mean +/- SEM' p < 0.05). After 6 h of reflow, i.e., at a time-point when the evoked calcium uptake is enhanced, theophylline had no effect on evoked [Ca2+]ec shifts. In summary, during ischemia the uptake of calcium into CA1 pyramidal cells started in the dendrites and preceded that in the cell bodies. Removal of adenosine inhibition by theophylline accelerated ischemic calcium uptake and enhanced electrically evoked calcium uptake in control animals. In contrast, in the postischemic phase adenosine inhibition was lost with a secondary enhancement of the evoked calcium uptake that may be one critical factor in the development of delayed neuronal death.
Andiné
P
P
Institute of Neurobiology, University of Göteborg, Sweden.
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008839:Microelectrodes; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D058914:Purinergic Antagonists; D011712:Pyramidal Tracts / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology
D005971:Glutamates; D058914:Purinergic Antagonists; D018698:Glutamic Acid; D013806:Theophylline; D000241:Adenosine; D002118:Calcium