Local anaesthetic bupivacaine alters function of sarcoplasmic reticulum and sarcolemmal vesicles from rabbit masseter muscle.
The effects of local anaesthetics, bupivacaine and lidocaine, on Ca2+ flux behaviour of sarcoplasmic reticulum and on sarcolemmal functions were studied in the rabbit masseter muscle. The experiments were performed on sarcoplasmic reticulum and sarcolemmal vesicles prepared at 1 to 10 days after injection of local anaesthetics or saline into masseter muscle as well as on sarcoplasmic reticulum vesicles prepared from non-treated rabbits (for assessment of the effect on in vitro incubation with local anaesthetics). Bupivacaine potently reduced the efficiency of active sarcoplasmic reticulum Ca2+ transport as evaluated by coupling ratio (Ca2+ transported/ATP hydrolyzed, in the presence of oxalate) at 3 days after the injection; there was only a slight degree of uncoupling of Ca2+ transport from ATP hydrolysis with lidocaine injection. Bupivacaine but not lidocaine, at 3 days after injection, decreased both the apparent permeability of sarcoplasmic reticulum vesicles to Ca2+, determined by measuring net efflux of Ca2+ after stopping pump-mediated fluxes, and the steady-state Ca2+ load in sarcoplasmic reticulum, but had no effect on overall turnover of the Ca2+ATPase. The effects of bupivacaine on apparent sarcoplasmic reticulum Ca2+ permeability and steady-state Ca2+ load were inhibited by a Ca2+ antagonist verapamil. The reduction of Ca2+ uptake of sarcoplasmic reticulum and the protective effect of verapamil were reproduced in unfractionated homogenates prepared at 3 days after bupivacaine injection. In vitro exposure of sarcoplasmic reticulum vesicles to bupivacaine (0.5 to 50 mM) reduced steady-state Ca2+ load in a dose-dependent manner. The observed effect elicited by bupivacaine (25 mM) was partially protected by procaine, an inhibitor of Ca2(+)-induced Ca2+ release from sarcoplasmic reticulum, or by specific closure of the sarcoplasmic reticulum Ca2+ release channel by ryanodine, suggesting the possibility that in vitro exposure of sarcoplasmic reticulum vesicles to bupivacaine may produce an increase in apparent permeability of sarcoplasmic reticulum to Ca2+. In sarcolemma, bupivacaine reduced Na+,K(+)-ATPase and Na(+)-Ca2+ exchange activities at 3 days after injection; the effects on sarcolemmal vesicles were prevented by verapamil. These results suggest that although the effects elicited by bupivacaine injection and the in vitro exposure to bupivacaine on steady-state Ca2+ load of sarcoplasmic reticulum vesicles were similar, the membrane properties of the vesicles from bupivacaine-treated masseter muscles and those from normal untreated muscles may not be the same, which indicates that pure bupivacaine effect is due partly by an effect on ryanodine- and procaine-sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)
Takahashi
S
S
Department of Pharmacology, Kanagawa Dental College, Japan.
D000779:Anesthetics, Local; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008406:Masseter Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000779:Anesthetics, Local; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D008012:Lidocaine; D012964:Sodium; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D002045:Bupivacaine