Isoflurane reduces the carbachol-evoked Ca2+ influx in neuronal cells

• Published in: Anesthesiology (Philadelphia) 2004-10, Vol.101 (4), p.895-901
• Main Authors: CORRALES, Alexandra, FANG XU, GARAVITO-AGUILAR, Zayra V, BLANCK, Thomas J. J, RECIO-PINTO, Esperanza
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Inhalation - pharmacology; Biological and medical sciences; Calcium - metabolism; Calcium Channels, L-Type - physiology; Calcium Channels, N-Type - physiology; Carbachol - pharmacology; Cell Line, Tumor; Humans; Isoflurane - pharmacology; Lanthanoid Series Elements - pharmacology; Medical sciences; Neurons - drug effects; Neurons - metabolism; Nitrendipine - pharmacology; omega-Conotoxin GVIA - pharmacology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200410000-00014

The authors previously reported that the isoflurane-caused reduction of the carbachol-evoked cytoplasmic Ca transient increase ([Ca]cyt) was eliminated by K or caffeine-pretreatment. In this study the authors investigated whether the isoflurane-sensitive component of the carbachol-evoked [Ca]cyt transient involved Ca influx through the plasma membrane. Perfused attached human neuroblastoma SH-SY5Y cells were exposed to carbachol (1 mm, 2 min) in the absence and presence of isoflurane (1 mm) and in the absence and presence of extracellular Ca (1.5 mm). The authors studied the effect of the nonspecific cationic channel blocker La (100 microm), of the L-type Ca channel blocker nitrendipine (10 microm), and of the N-type Ca channel blocker omega-conotoxin GVIA (0.1 microm) on isoflurane modulation of the carbachol-evoked [Ca]cyt transient. [Ca]cyt was detected with fura-2 and experiments were carried out at 37 degrees C. Isoflurane reduced the peak and area of the carbachol-evoked [Ca]cyt transient in the presence but not in the absence of extracellular Ca. La had a similar effect as the removal of extracellular Ca. Omega-conotoxin GVIA and nitrendipine did not affect the isoflurane sensitivity of the carbachol response although nitrendipine reduced the magnitude of the carbachol response. The current data are consistent with previous observations in that the carbachol-evoked [Ca]cyt transient involves both Ca release from intracellular Ca stores and Ca entry through the plasma membrane. It was found that isoflurane attenuates the carbachol-evoked Ca entry. The isoflurane sensitive Ca entry involves a cationic channel different from the L- or N- type voltage-dependent Ca channels. These results indicate that isoflurane attenuates the carbachol-evoked [Ca]cyt transient at a site at the plasma membrane that is distal to the muscarinic receptor.