CA2-DEPENDENT AND PH-DEPENDENT HALOTHANE STIMULATION OF CA2+ RELEASE IN SARCOPLASMIC-RETICULUM FROM FROG-MUSCLE()

The effect of halothane on calcium release kinetics was studied in tri ad-enriched sarcoplasmic reticulum vesicles from frog skeletal muscle. Release from vesicles passively equilibrated with 3 mM (CaCl2)-Ca-45 was measured in the millisecond time range by use of a fast-filtration system. Halothane (400 mu M) increased release rate constants at pH 7 .1 and 7.4 as a function of extravesicular pCa. In contrast, halothane at pH 6.8 produced the same stimulation of release from pCa 7.0 to 3. 0; no release took place in these conditions in the absence of halotha ne. Halothane shifted the calcium activation curve at pH 7.1, bat not at pH 7.4, to the left and increased channel open probability at pH 7. 1 in the cis pCa range of 7.0 to 5.0. These results indicate that cyto solic pCa and pH modulate the stimulatory effects of halothane on calc ium release. Furthermore. halothane stimulated release in frog skeleta l muscle at low pH and resting calcium concentration, indicating that in frog muscle halothane can override the closing of the release chann els produced by these conditions, as it does in malignant hyperthermia -susceptible porcine muscle.