Effect of halothane on K+ and carbachol stimulated [3H]noradrenaline release and increased [Ca2+]i in SH-SY5Y human neuroblastoma cells.
We have examined the effects of the volatile general anaesthetic agent, halothane, on K+ and carbachol stimulated [3H]noradrenaline release and associated increases in intracellular Ca2+ in a cultured human neuroblastoma cell line, SH-SY5Y. K+ (but not carbachol) stimulated [3H]noradrenaline release, and the increase in intracellular Ca2+ concentration was entirely extracellular Ca2+ dependent. Halothane produced a dose-dependent reduction in K+ evoked release of [3H]noradrenaline with significant inhibition (17%) occurring from 1.26 atm%. Basal and carbachol evoked release were unaffected. Halothane also produced a dose-dependent reduction in K+ evoked increases (measured at the peak) in intracellular Ca2+ with significant inhibition (29%) occurring from 0.88 atm%. K+ plateau, basal and carbachol evoked increases in intracellular Ca2+ were unaffected. These data suggest that halothane reduced Ca2+ entry through voltage-sensitive Ca2+ channels and implicate this important class of ion channel in the mechanism of anaesthesia.
Atcheson
R
R
University Department of Anaesthesia, Leicester Royal Infirmary.
Bjornstrom
K
K
Hirst
R A
RA
Rowbotham
D J
DJ
Lambert
D G
DG
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018685:Anesthetics, Inhalation; D002217:Carbachol; D011188:Potassium; D002118:Calcium; D006221:Halothane; D009638:Norepinephrine