Volatile anesthetics increase intracellular calcium in cerebrocortical and hippocampal neurons.
BACKGROUND
An increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic-induced increases in [Ca2+]i conflict.


METHODS
Changes in [Ca2+]i were measured using fura-2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 microM isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+-free medium, in the presence of Ca2+-channel blockers, and in the presence of the Ca2+-release inhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single-dose experiments in CA1 neurons in hippocampal slices with halothane (360 microM) and in acutely dissociated CA1 neurons with halothane (360 microM) and isoflurane (445 microM) also were performed.


RESULTS
Isoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]i in cortical slices in a dose-dependent manner (P < 0.05). This increase was not altered by Ca2+-channel blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic 1,2-dichlorohexafluorocyclobutane did not increase [Ca2+]i. In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca2+]i by 15 nM (P < 0.05). Halothane increased [Ca2+]i in dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05).


CONCLUSIONS
(1) Isoflurane and halothane reversibly increase [Ca2+]i in isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]i is caused primarily by release from intracellular stores. (3) Increases in [Ca2+]i occur with anesthetics but not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.
Kindler
C H
CH
Department of Anesthesia, University of California, San Francisco 94143-0542, USA.
Eilers
H
H
Donohoe
P
P
Ozer
S
S
Bickler
P E
PE
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D002118:Calcium; D006221:Halothane