Thiopental inhibits increases in [Ca2+]i induced by membrane depolarization, NMDA receptor activation, and ischemia in rat hippocampal and cortical slices.
BACKGROUND
This study examined the effects of thiopental on intracellular calcium ([Ca2+]i) changes induced by membrane depolarization, N-methyl-D-aspartate (NMDA) receptor activation, and ischemia.


METHODS
Experiments were performed in brain slices prepared from Wistar rats. [Ca2+]i measurements were taken on the CA1 pyramidal cell layer of the hippocampus or layers II to III of the somatosensory cortex using the fura-2 fluorescence technique. Membrane depolarization and NMDA receptor activation were induced by exposing slices to 60 mM K+ and 100 microM NMDA, respectively. In vitro ischemia was induced by superfusing slices with glucose-free Krebs solution equilibrated with 95% nitrogen and 5% carbon dioxide. Thiopental was applied 5 min before application of high K+ and NMDA, or before in vitro ischemia.


RESULTS
Ischemia for 15 min produced a characteristic [Ca2+]i increase in both hippocampal and cortical slices. Thiopental prolonged the latency to the appearance of the [Ca2+]i plateau and reduced the magnitudes of increase in [Ca2+]i 8, 10, and 15 min after the onset of ischemia. Thiopental also suppressed the high K+- and NMDA-induced [Ca2+]i increases. The NMDA-induced [Ca2+]i increases were attenuated to a greater extent in cortical slices than were those in hippocampal slices. The inhibition of thiopental on the 200-microM NMDA-mediated [Ca2+]i response was confirmed in cultured cortical neurons.


CONCLUSIONS
The results indicate that thiopental attenuates ischemia-induced [Ca2+]i increases in the hippocampus and cortex in vitro, probably because of its inhibition of both voltage-gated calcium channels and NMDA receptors. The regionally different inhibition of thiopental on NMDA receptors may relate to its region-specific action against ischemia.
Department of Anesthesiology, Niigata University School of Medicine, Japan. anesth@med.niigata-u.ac.jp
R Z
RZ
Zhan
N
N
Fujiwara
H
H
Endoh
T
T
Yamakura
K
K
Taga
S
S
Fukuda
K
K
Shimoji
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D016257:Fura-2; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*; D013874:Thiopental / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D016194:Receptors, N-Methyl-D-Aspartate; D005947:Glucose; D013874:Thiopental; D002118:Calcium; D016257:Fura-2