Relative potencies of volatile anesthetics in altering the kinetics of ion channels in BC3H1 cells.

Single channel recording techniques have been used to study effects of the volatile anesthetics enflurane, halothane, isoflurane and methoxyflurane, and the gaseous agent nitrous oxide, on the properties of nicotinic channels activated by acetylcholine. Single channel currents activated by 250 nM acetylcholine were recorded from cell-attached patches of BC3H1 mouse tumor cells grown in culture. All of the potent volatile agents shortened the duration of individual opening events and caused openings to appear grouped together in bursts. The slower time constant of channel open-time distributions was decreased 50% by approximately 0.22% enflurane (0.12 mM), 0.25% isoflurane (0.10 mM), 0.30% halothane (0.16 mM), 0.076% methoxyflurane (0.21 mM) or 80% nitrous oxide (20 mM) at room temperature. Even when values were corrected to 37 degrees C, the concentrations required to decrease channel open time are less than clinical dosages. Anesthetic potency in altering channel properties was directly related to both clinical potency and lipid solubility, although those agents with greater clinical potencies required relatively higher concentrations to reduce channel open time. Results are interpreted in terms of a simple sequential channel blocking model, a sequential blocking model in which anesthetics also enhance the rate at which open channels normally close, and a cyclic blocking model in which blocked channels may close directly without having to pass back through the open state. All of the agents appeared to act in a qualitatively similar fashion and no differences were found that could account for the differing clinical profiles of the volatile anesthetics.