Effect of halothane on intracellular calcium oscillations in porcine tracheal smooth muscle cells.

Abstract

The effect of halothane on intracellular Ca2+ concentration ([Ca2+]i) regulation in porcine tracheal smooth muscle cells was examined with real-time confocal microscopy. Both 1 and 2 minimum alveolar concentration (MAC) halothane increased basal [Ca2+]i when Ca2+ influx and efflux were blocked, suggesting increased sarcoplasmic reticulum (SR) Ca2+ leak and/or decreased reuptake. In beta-escin-permeabilized cells, heparin inhibition of inositol 1,4, 5-trisphosphate-receptor channels blunted the halothane-induced increase in [Ca2+]i. Both 1 and 2 MAC halothane decreased the frequency and amplitude of ACh-induced [Ca2+]i oscillations (which represent SR Ca2+ release through ryanodine-receptor channels), abolishing oscillations in approximately 20% of tracheal smooth muscle cells at 2 MAC. When Ca2+ influx and efflux were blocked, halothane increased the baseline and decreased the frequency and amplitude of [Ca2+]i oscillations, inhibiting oscillations in approximately 70% of cells at 2 MAC. The fall time of [Ca2+]i oscillations and the rate of fall of the [Ca2+]i response to caffeine were both increased by halothane. These results suggest that halothane abolishes agonist-induced [Ca2+]i oscillations by 1) depleting SR Ca2+ via increased Ca2+ leak through inositol 1,4, 5-trisphosphate-receptor channels, 2) decreasing Ca2+ release through ryanodine-receptor channels, and 3) inhibiting reuptake.