Effect of bupivacaine enantiomers on Ca(2+) release from sarcoplasmic reticulum in skeletal muscle.

摘要

Local anesthetics affect intracellular Ca(2+) movement in the myocyte. The use of isomers may help to reveal specific mechanisms of action, such as receptor mediation. In the present study, we used skinned fibers from mammalian skeletal muscle to test whether bupivacaine enantiomers had different effects on Ca(2+) release and uptake by the sarcoplasmic reticulum, and on the Ca(2+) sensitivity of the contractile system. Ca(2+)-induced Ca(2+) release was enhanced by S-bupivacaine 1 approximately 3 mM, but inhibited by R-bupivacaine 3 mM, remaining unaffected at lower doses. These enantiomers inhibited Ca(2+) uptake to different degrees, with R-bupivacaine having a stronger effect. Ca(2+) sensitivity of the contractile system was equally enhanced by R- and S-bupivacaine. These findings might help to explain the myoplasmic Ca(2+) elevation induced by bupivacaine. The observed stereoselectivity suggests effects on specific proteins, the ryanodine Ry(1) receptor and the Ca(2+)-ATPase pump, rather than non-specific increase in Ca(2+) permeability.