Interaction of extracellular albumin and intravenous anaesthetics, etomidate and propofol, on calcium signalling in rat airway smooth muscle cells

It has been shown in vitro that general anaesthetics modify airway responsi veness via, at least partially, a direct inhibitory effect on calcium signa lling in airway smooth muscle cells. However, in vivo, these anaesthetic co mpounds bind serum proteins. We have investigated the effect of exposure to extracellular albumin of freshly isolated airway smooth muscle cells on th e propofol- and etomidate-induced inhibitory effect on calcium signalling. [Ca2+](i) was measured by microspectrofluorimetry in rat isolated tracheal smooth muscle cells using the fluorescent dye indo-1. Propofol (3 x 10(-4) M) and etomidate (10(-4) M) were the lowest 'effective' concentrations that altered the [Ca2+](i) response. This alteration consisted of a decrease in both the amplitude of the [Ca2+](i) peak (from 358 +/- 13 nM to 65 +/- 15 and 108 +/- 27 nM fur propofol and etomidate, respectively) and the percent age of responding cells (from 80% to 37 and 25%, respectively) in response to the low concentration of ACh and a decrease in the Ca2+ oscillation freq uency (from 9.9 +/- 0.3 min(-1) to 4.7 +/- 0.4 and 6.9 +/- 0.4 min(-1), res pectively) in response to the high concentration of ACh. Increasing the con centration of albumin reduced the inhibitory effect of etomidate and propof ol on the [Ca2+](i) response to ACh. When extracellular albumin concentrati on was kept constant (20 g/L), increasing the concentration of etomidate by one log restored its inhibitory effect on the calcium signal. This study i ndicates that increasing the concentration of extracellular albumin reduces the inhibitory effect of intravenous anaesthetics on calcium signalling in airway smooth muscle cells. This report suggests that, in extrapolating in vitro dose response relationships to those From in vivo conditions, the ef fect of the concentration of extracellular protein can be estimated. (C) 20 00 Editions scientifiques et medicales Elsevier SAS.