Halothane and isoflurane augment depolarization-induced cytosolic CA2+ transients and attenuate carbachol-stimulated CA2+ transients.
BACKGROUND
Neuronal excitability is in part determined by Ca2+ availability that is controlled by regulatory mechanisms of cytosolic Ca2+ ([Ca2+]cyt). Alteration of any of those mechanisms by volatile anesthetics (VAs) may lead to a change in presynaptic transmission and postsynaptic excitability. Using a human neuroblastoma cell line, the effects of halothane and isoflurane on cytosolic Ca2+ concentration ([Ca2+]cyt) in response to K+ and carbachol stimulation were investigated.


METHODS
Volatile anesthetic (0.05-1 mm) action on stimulated [Ca2+]cyt transients were monitored in suspensions of SH-SY5Y cells loaded with fura-2. Potassium chloride (KCl; 100 mm) was used to depolarize and activate Ca2+ entry through voltage-dependent calcium channels; 1 mm carbachol was used to activate muscarinic receptor-mediated inositol triphosphate (IP3)-dependent intracellular Ca2+ release. Sequential stimulations, KCl followed by carbachol and vice versa, were used to investigate interactions between intracellular Ca2+ stores.


RESULTS
Halothane and isoflurane in clinically relevant concentrations enhanced the K+-evoked [Ca2+]cyt transient whether intracellular Ca2+ stores were full or partially depleted. In contrast, halothane and isoflurane reduced the carbachol-evoked [Ca2+]cyt transient when the intracellular Ca2+ stores were full but had no effect when the Ca2+ stores were partially depleted by KCl stimulation.


CONCLUSIONS
Volatile anesthetics acted on sites that differently affect the K+- and carbachol-evoked [Ca2+]cyt transients. These data suggest the involvement of an intracellular Ca2+ translocation from the caffeine-sensitive Ca2+ store to the inositol triphosphate-sensitive Ca2+ store that was altered by halothane and isoflurane.
Xu
F
F
Department of Anesthesiology, The Hospital for Special Surgery, New York, New York 10021, USA.
Zhang
J
J
Recio-Pinto
E
E
Blanck
T J
TJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D005456:Fluorescent Dyes; D016257:Fura-2; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018685:Anesthetics, Inhalation; D005456:Fluorescent Dyes; D018721:Muscarinic Agonists; D011189:Potassium Chloride; D002217:Carbachol; D007530:Isoflurane; D002118:Calcium; D016257:Fura-2; D006221:Halothane