Transient increases of intracellular Ca2+ induced by volatile anesthetics in rat hepatocytes.
The affects of volatile anesthetics on mobilization of intracellular Ca2+ was monitored in primary cultures of rat hepatocytes using the fluorescent Ca2+ probe Fura-2. The use of Fura-2 was limited by several factors which complicated the quantitative analysis of the results, such as: (i) a high rate of dye leakage; (ii) changes in the redox state of the hepatocytes which interfered with the fluorescence produced by the dye at various excitation wavelengths; (iii) compartmentalization of the dye producing high local intracellular concentrations; and, of particular importance for this study, (iv) enhanced photobleaching of the dye in the presence of halothane. To aid in the interpretation of the Fura-2 data, the Ca2(+)-sensitive photoprotein aequorin was also used to monitor changes in [Ca2+]i. The aequorin and Fura-2 techniques qualitatively yielded the same result, that the volatile anesthetic agents halothane, enflurane, and isoflurane induce an immediate and transient increase of [Ca2+]i. The durations of these transients were approximately between 5 and 10 min and were not related to any evident acute cell toxicity. The [Ca2+]i increases induced by the volatile anesthetic agents were dose-dependent, with halothane the most potent. The exact mechanism governing these increases in [Ca2+]i induced by these anesthetics in rat hepatocytes is unknown, but is likely to involve effects on both the cell surface membrane and endoplasmic reticulum components of the signal transducing system.
Iaizzo
P A
PA
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
Olsen
R A
RA
Seewald
M J
MJ
Powis
G
G
Stier
A
A
Van Dyke
R A
RA
D000331:Aequorin / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004737:Enflurane / Q000494:pharmacology; D016257:Fura-2 / Q000378:metabolism / Q000528:radiation effects; D006221:Halothane / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010777:Photochemistry; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology
D000777:Anesthetics; D014667:Vasopressins; D000331:Aequorin; D015759:Ionomycin; D004737:Enflurane; D007530:Isoflurane; D002118:Calcium; D016257:Fura-2; D006221:Halothane