Isoflurane reduction of carbachol-evoked cytoplasmic calcium transients is dependent on caffeine-sensitive calcium stores.

Abstract

BACKGROUND:

Many muscarinic functions are relevant to anesthesia, and alterations in muscarinic activity affect the anesthetic/analgesic potency of various drugs. Volatile anesthetics have been shown to depress muscarinic receptor function, and inhibition of the muscarinic signaling pathway alters the minimal alveolar anesthetic concentration of inhaled anesthetics. The purpose of this investigation was to determine in a neuronal cell which source of Ca2+ underlying the carbachol-evoked transient increase in cytoplasmic Ca2+ was reduced by isoflurane.

METHODS:

Experiments were performed at 37 degrees C on continuously perfused monolayers of human neuroblastoma SH-SY5Y cells using Fura-2 as the cytoplasmic Ca2+ indicator. Carbachol (1 mm) was applied to evoke a transient increase in cytoplasmic Ca2+.

RESULTS:

Isoflurane (1 mm) reduces the carbachol-evoked transient increase in cytoplasmic Ca2+, and this isoflurane action is eliminated when the cells are continuously stimulated with 200 mm KCl or pretreated with 10 mm caffeine or 200 microm ryanodine.

CONCLUSIONS:

Isoflurane reduction of the carbachol-evoked transient increase in cytoplasmic Ca2+ requires full caffeine-sensitive Ca2+ stores and Ca2+ release from the caffeine-sensitive stores through the ryanodine-sensitive Ca2+ release channels. The results indicate that isoflurane interferes with a muscarinic Ca2+ signaling through a mechanism downstream from the muscarinic receptors.

• Authors: Alexandra Corrales, Fang Xu, Zayra Garavito-Aguilar, Thomas J J Blanck, Esperanza Recio-Pinto
• Journal: Anesthesiology (Anesthesiology) Vol. 99 Issue 4 Pg. 882-8 (Oct 2003) ISSN: 0003-3022 [Print] United States
• PMID: 14508321 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channels
• Caffeine
• Carbachol
• Isoflurane
• Calcium

Topics

• Caffeine (pharmacology)
• Calcium (metabolism)
• Calcium Channels (metabolism)
• Carbachol (antagonists & inhibitors, pharmacology)
• Cytoplasm (drug effects, physiology)
• Drug Interactions (physiology)
• Humans
• Isoflurane (pharmacology)
• Tumor Cells, Cultured