Abstract
We examined the effect of halothane on Ca-ATPase activity and its partial reactions of fragmented sarcoplasmic reticulum from bullfrog skeletal muscle (frog FSR) and compared them with the effects of caffeine in order to make it clear whether the effect on ATPase activity is related to the release of Ca or the inhibition of Ca uptake. The effect of halothane on the Ca-ATPase reaction of frog FSR was also compared with that of rabbit FSR. 1. Halothane decreased the apparent affinity for Ca 2+ of Ca-ATPase activity of frog FSR. Procaine reversed this effect only slightly. Experiments simultaneously determining the Ca-ATPase activity and the EP level revealed that the drug did not affect the rate of EP hydrolysis, and that its main action must be on the steps leading to EP formation with a reduced apparent affinity for Ca 2+ . The changes in ATP-ADP exchange rate can be explained largely by these effects. Halothane reduced ATP binding to FSR. 2. With intact rabbit FSR, halothane caused an increase in Ca-ATPase activity in the presence of high concentrations of Ca 2+ , in addition to reducing the apparent affinity for Ca 2+ . However, the augmentation by halothane was not observed in the presence of A23187. The effects of halothane on rabbit FSR are essentially similar to those on frog FSR. 3. In contrast to halothane, caffeine increased the Ca-ATPase activity of frog FSR at limited range of Ca 2+ concentrations in the presence of 4 m m Mg 2+ . This effect was Mg 2+ dependent: in the presence of 4 m m Mg 2+ no change in ATPase activity was observed. Caffeine exerted little effect if any on the ATP-ADP exchange rate. 4. The results mentioned above and other lines of evidence suggest that the effect of halothane on Ca-ATPase activity or its partial reactions should be related to the inhibition of Ca uptake rather than the Ca releasing action.