Intracellular Mechanism of Action of Isoflurane and Halothane on Striated Muscle of the Rabbit.

Su, Judy Y. PhD; Bell, Janet G. BS
Anesthesia & Analgesia: May 1986

Studies were conducted on the effects of isoflurane and halothane on intracellular mechanisms of striated muscle contraction: Ca2+ activation of the contractile proteins and Ca2+ uptake and release from the sarcoplasmic reticulum. Functionally skinned muscle fibers (sarcolemma disrupted by homogenization) from isolated papillary muscle (PM), soleus (SL) (slow-twitch skeletal muscle), and adductor magnus (AM) (fast-twitch skeletal muscle) of rabbits were mounted on a photodiode tension transducer. They were immersed in control solution (saturated with N2), then in test solution (saturated with anesthetic-N2 mixture), and in control solution again. The following two studies were carried out: 1) in the study of Ca2+-activated tension development of the contractile proteins, free Ca2+ concentration in the bathing solution was controlled by the use of a high EGTA (7 mM), and 2) in the study of Ca2+ uptake and release from the sarcoplasmic reticulum (SR), Ca2+ was loaded into the SR and released with caffeine and the resulting tension transients were measured. Isoflurane (1-4%) decreased (6-9%) the maximal Ca2+-activated tension development in PM and SL but more in PM than in SL. In AM, however, isoflurane and halothane (1-3%) produced no change. Isoflurane decreased submaximal Ca2+ -activated tension development in PM, but effected no change in it in SL. Isoflurane and halothane increased the tension development in AM to the extent of producing a shift to the left in the pCa-tension curves of <= 0.1 pCa unit. Isoflurane decreased by 16% Ca2+ uptake by the SR in PM at 3% concentration, increased uptake 110-143% in SL at 1-3%, and increased by 72-121% and 15-73% Ca2+ release from the SR in SL and AM, respectively. With submaximal caffeine concentration at 2 mM, isoflurane (4% only) increased by 21% Ca2+ release from the sarcoplasmic reticulum in PM. Halothane (1-3%) decreased by 19-37% Co2+ uptake and increased by 38-75% Ca2+ release from the SR in skinned fibers of AM. We conclude that isoflurane and halothane have similar intracellular mechanisms of action in striated muscle. Isoflurane-induced decreases in submaximal and maximal Ca2+-activated tension development and in Ca2+ uptake by the sarcoplasmic reticulum in PM could partially contribute to decreased myocardial contractility. The increases in Ca2+ release from the SR produced by isoflurane and halothane in SL and AM could contribute to increased muscle contraction.

(C) 1986 International Anesthesia Research Society