ABSTRACT
Local anesthetics affect intracellular Ca2+ 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 Ca2+ release and uptake by the sarcoplasmic reticulum, and on the Ca2+ sensitivity of the contractile system. Ca2+-induced Ca2+ 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 Ca2+ uptake to different degrees, with R-bupivacaine having a stronger effect. Ca2+ sensitivity of the contractile system was equally enhanced by R- and S-bupivacaine. These findings might help to explain the myoplasmic Ca2+ elevation induced by bupivacaine. The observed stereoselectivity suggests effects on specific proteins, the ryanodine Ry1 receptor and the Ca2+-ATPase pump, rather than non-specific increase in Ca2+ permeability.