Differential Effects of Sevoflurane, Isoflurane, and Halothane on Ca (2+) Release from the Sarcoplasmic Reticulum of Skeletal Muscle 

1999 ◽  
Vol 91 (1) ◽  
pp. 179-186 ◽  
Author(s):  
Gudrun Kunst ◽  
Bernhard M. Graf ◽  
Rupert Schreiner ◽  
Eike Martin ◽  
Rainer H. A. Fink
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Muscle Fibers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Maximal Force ◽  
Skinned Muscle ◽  
Skeletal Muscle Fibers ◽  
Force Relation ◽  
The Individual

Background Although malignant hyperthermia after application of sevoflurane has been reported, little is known about its action on intracellular calcium homeostasis of skeletal muscle. The authors compared the effect of sevoflurane with that of isoflurane and halothane on Ca2+ release of mammalian sarcoplasmic reticulum and applied a novel method to quantify Ca2+ turnover in permeabilized skeletal muscle fibers. Methods Liquid sevoflurane, isoflurane, and halothane at 0.6 mM, 3.5 mM, and 7.6 mm were diluted either in weakly calcium buffered solutions with no added Ca2+ (to monitor Ca2+ release) or in strongly Ca2+ buffered solutions with [Ca2+] values between 3 nM and 24.9 microm for [Ca+]-force relations. Measurements were taken on single saponin skinned muscle fiber preparations of BALB/c mice. Individual [Ca2+]force relations were characterized by the Ca2+ concentration at half-maximal force that indicates the sensitivity of the contractile proteins and by the steepness. Each force transient was transformed directly into a Ca2+ transient with respect to the individual [Ca2+]-force relation of the fiber. Results At 0.6 mM, single force transients induced by sevoflurane were lower compared with equimolar concentrations of isoflurane and halothane (P < 0.05). Similarly, calculated peak Ca2+ transients of sevoflurane were lower than those induced by equimolar halothane (P < 0.05). The Ca2+ concentrations at half maximal force were decreased after the addition of sevoflurane, isoflurane, and halothane in a concentration-dependent manner (P < 0.05). Conclusion Whereas sevoflurane, isoflurane, and halothane similarly increase the Ca2+ sensitivity of the contractile apparatus in skeletal muscle fibers, 0.6 mM sevoflurane induces smaller Ca2+ releases from the sarcoplasmic reticulum than does equimolar halothane.

Desflurane Induces Only Minor Ca2+Release from the Sarcoplasmic Reticulum of Mammalian Skeletal Muscle

2000 ◽  
Vol 93 (3) ◽  
pp. 832-836 ◽  
Author(s):  
Gudrun Kunst ◽  
Astrid G. Stucke ◽  
Bernhard M. Graf ◽  
Eike Martin ◽  
Rainer H. A. Fink
Keyword(s):  
Skeletal Muscle ◽  
Calcium Release ◽  
Muscle Fibers ◽  
Mammalian Skeletal Muscle ◽  
Skinned Muscle ◽  
Skeletal Muscle Fibers ◽  
Force Relation ◽  
The Individual ◽  
Few Data ◽  
Sensitizing Effect

Background Desflurane is a weaker trigger of malignant hyperthermia than is halothane. There are very few data of the pathophysiologic background of this observation. Therefore, the authors' aim was to investigate the direct effect of desflurane on calcium release in skinned skeletal muscle fibers. Methods For the measurements, single saponin-skinned muscle fiber preparations of BALB/c mice were used. For Ca2+ release experiments, liquid desflurane at 0.6 and 3.5 mm was applied to weakly calcium-buffered solutions with no added Ca2+. Desflurane was diluted in strongly Ca2+-buffered solutions, with [Ca2+] between 3.0 and 24.9 micrometer for [Ca2+]-force relations. Force transients were transformed into Ca2+ transients based on the individual [Ca2+]-force relations. As controls, 30 mm caffeine and equimolar sevoflurane were investigated in the same muscle fibers. Results At 3.5 mm, desflurane induced peak force transients of 8 +/- 4% (mean +/- SD) of maximal Ca2+-activated force (Tmax). These peak values were significantly smaller than those in the presence of 3.5 mm sevoflurane (24 +/- 10% of Tmax, P < 0.05), and 4 or 5 times smaller than previously reported Ca2+-release-induced force transients by equimolar halothane. Calculated peak Ca2+ transients derived from force transients and induced by 3.5 and 0.6 mm desflurane were significantly smaller than those induced by 30 mm caffeine. The [Ca2+]-force relation was shifted by desflurane, resulting in a Ca2+-sensitizing effect. The maximal Ca2+-activated force was significantly increased by 0.6 mm desflurane in comparison with the control, with no added substance (P </= 0.05). Conclusion Desflurane induces only slight Ca2+ release in skinned skeletal muscle fibers.

scholarly journals Calcium-gated calcium channels in sarcoplasmic reticulum of rabbit skinned skeletal muscle fibers.

1986 ◽  
Vol 87 (2) ◽  
pp. 289-303 ◽  
Author(s):  
P Volpe ◽  
G Salviati ◽  
A Chu
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Ruthenium Red ◽  
Scattering Method ◽  
Tension Development ◽  
Maximal Force ◽  
Skeletal Muscle Fibers ◽  
Ca2 Channels

The action of ruthenium red (RR) on Ca2+ loading by and Ca2+ release from the sarcoplasmic reticulum (SR) of chemically skinned skeletal muscle fibers of the rabbit was investigated. Ca2+ loading, in the presence of the precipitating anion pyrophosphate, was monitored by a light-scattering method. Ca2+ release was indirectly measured by following tension development evoked by caffeine. Stimulation of the Ca2+ loading rate by 5 microM RR was dependent on free Ca2+, being maximal at pCa 5.56. Isometric force development induced by 5 mM caffeine was reversibly antagonized by RR. IC50 for the rate of tension rise was 0.5 microM; that for the extent of tension was 4 microM. RR slightly shifted the steady state isometric force/pCa curve toward lower pCa values. At 5 microM RR, the pCa required for half-maximal force was 0.2 log units lower than that of the control, and maximal force was depressed by approximately 16%. These results suggest that RR inhibited Ca2+ release from the SR and stimulated Ca2+ loading into the SR by closing Ca2+-gated Ca2+ channels. Previous studies on isolated SR have indicated the selective presence of such channels in junctional terminal cisternae.

Differential Effects of Bupivacaine and Ropivacaine Enantiomers on Intracellular Ca2+Regulation in Murine Skeletal Muscle Fibers

2005 ◽  
Vol 102 (4) ◽  
pp. 793-798 ◽  
Author(s):  
Wolfgang Zink ◽  
Goetz Missler ◽  
Barbara Sinner ◽  
Eike Martin ◽  
Rainer H. A. Fink ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Local Anesthetic ◽  
Muscle Fibers ◽  
Optical Isomers ◽  
Skinned Muscle ◽  
Skeletal Muscle Fibers ◽  
Racemic Mixtures ◽  
Intracellular Ca ◽  
Murine Skeletal Muscle

Background Increased intracellular Ca concentrations are considered to be a major pathomechanism in local anesthetic myotoxicity. Racemic bupivacaine and S-ropivacaine cause Ca release from the sarcoplasmic reticulum of skeletal muscle fibers and simultaneously inhibit Ca reuptake. Examining the optical isomers of both agents, the authors investigated stereoselective effects on muscular Ca regulation to get a closer insight in subcellular mechanisms of local anesthetic myotoxicity. Methods R- and S-enantiomers as well as racemic mixtures of both agents were tested in concentrations of 1, 5, 10, and 15 mm. Saponin-skinned muscle fibers from the extensor digitorum longus muscle of BALB/c mice were examined according to a standardized procedure. For the assessment of effects on Ca uptake and release from the sarcoplasmic reticulum, agents were added to the loading solution and the release solution, respectively, and force and Ca transients were monitored. Results The effects of S-enantiomers on both Ca release and reuptake were significantly more pronounced than those of racemic mixtures and R-enantiomers, respectively. In addition, the effects of racemates were markedly stronger than those of R-enantiomers. With regard to Ca release, the effects of bupivacaine isomers were more pronounced than the isomers of ropivacaine. Conclusions These data show that stereoselectivity is involved in alterations of intracellular Ca regulation by bupivacaine and ropivacaine. S-enantiomers seem to be more potent than R-enantiomers, with intermediate effects of racemic mixtures. In addition, lipophilicity also seems to determine the extent of Ca release by local anesthetics.

Functional effects of uridine triphosphate on human skinned skeletal muscle fibers

1998 ◽  
Vol 76 (2) ◽  
pp. 110-117 ◽  
Author(s):  
R Vianna-Jorge ◽  
C F Oliveira ◽  
Y Mounier ◽  
G Suarez-Kurtz
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Muscle Fibers ◽  
Fiber Types ◽  
Release Channel ◽  
Uridine Triphosphate ◽  
Skinned Muscle ◽  
Skeletal Muscle Fibers ◽  
Slow Type ◽  
Relationship Of

Chemically skinned human skeletal muscle fibers were used to study the effects of uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship to the left along the abcissae and increased maximum Ca2+-activated tension, both effects being larger in slow- than in fast-type fibers; (ii) markedly reduced Ca2+ uptake by the SR (evaluated by the caffeine-evoked tension) in both fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow- but not in fast-type fibers. The effects on the SR functional properties are consistent with the notion that UTP is a poor substitute for ATP as a substrate for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca2+-release channel. The UTP-induced tension in human slow-type fibers is attributed to effect(s) of the nucleotide on the tension-pCa relationship of the contractile machinery. The present data reveal important differences between the effects of UTP on human versus rat muscle fibers.Key words: skinned muscle fiber, UTP-induced tension, tension-pCa relationship, sarcoplasmic reticulum, calcium transport.

Evidence for Na+/Ca2+exchange in intact single skeletal muscle fibers from the mouse

1998 ◽  
Vol 274 (4) ◽  
pp. C940-C946 ◽  
Author(s):  
Christopher D. Balnave ◽  
David G. Allen
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Muscle Fibers ◽  
Exchange Mechanism ◽  
Initial Exposure ◽  
Mouse Skeletal Muscle ◽  
Reverse Mode ◽  
Skeletal Muscle Fibers ◽  
Plateau Level ◽  
Sustained Increase

The myoplasmic free Ca2+concentration ([Ca2+]i) was measured in intact single fibers from mouse skeletal muscle with the fluorescent Ca2+ indicator indo 1. Some fibers were perfused in a solution in which the concentration of Na+ was reduced from 145.4 to 0.4 mM (low-Na+solution) in an attempt to activate reverse-mode Na+/Ca2+exchange (Ca2+ entry in exchange for Na+ leaving the cell). Under normal resting conditions, application of low-Na+ solution only increased [Ca2+]iby 5.8 ± 1.8 nM from a mean resting [Ca2+]iof 42 nM. In other fibers, [Ca2+]iwas elevated by stimulating sarcoplasmic reticulum (SR) Ca2+ release with caffeine (10 mM) and by inhibiting SR Ca2+ uptake with 2,5-di( tert-butyl)-1,4-benzohydroquinone (TBQ; 0.5 μM) in an attempt to activate forward-mode Na+/Ca2+exchange (Ca2+ removal from the cell in exchange for Na+ influx). These two agents caused a large increase in [Ca2+]i, which then declined to a plateau level approximately twice the baseline [Ca2+]iover 20 min. If the cell was allowed to recover between exposures to caffeine and TBQ in a solution in which Ca2+ had been removed, the increase in [Ca2+]iduring the second exposure was very low, suggesting that Ca2+ had left the cell during the initial exposure. Application of caffeine and TBQ to a preparation in low-Na+ solution produced a large, sustained increase in [Ca2+]iof ∼1 μM. However, when cells were exposed to caffeine and TBQ in a low-Na+ solution in which Ca2+ had been removed, a sustained increase in [Ca2+]iwas not observed, although [Ca2+]iremained higher and declined slower than in normal Na+ solution. This suggests that forward-mode Na+/Ca2+exchange contributed to the fall of [Ca2+]iin normal Na+ solution, but when extracellular Na+ was low, a prolonged elevation of [Ca2+]icould activate reverse-mode Na+/Ca2+exchange. The results provide evidence that skeletal muscle fibers possess a Na+/Ca2+exchange mechanism that becomes active in its forward mode when [Ca2+]iis increased to levels similar to that obtained during contraction.

scholarly journals Steady State Relation between Cytoplasmic Free Ca2+ Concentration and Force in Intact Frog Skeletal Muscle Fibers

1998 ◽  
Vol 111 (4) ◽  
pp. 505-519 ◽  
Author(s):  
Masato Konishi ◽  
Masaru Watanabe
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Skinned Fibers ◽  
Hill Coefficient ◽  
Experimental Conditions ◽  
Skeletal Muscle Fibers ◽  
Force Relation ◽  
Series Of Experiments

The steady state relation between cytoplasmic Ca2+ concentration ([Ca2+]i) and force was studied in intact skeletal muscle fibers of frogs. Intact twitch fibers were injected with the dextran-conjugated Ca2+ indicator, fura dextran, and the fluorescence signals of fura dextran were converted to [Ca2+]i using calibration parameters previously estimated in permeabilized muscle fibers (Konishi and Watanabe. 1995. J. Gen. Physiol. 106:1123–1150). In the first series of experiments, [Ca2+]i and isometric force were simultaneously measured during high K+ depolarization. Slow changes in [Ca2+]i and force induced by 15–30 mM K+ appeared to be in equilibrium, as instantaneous [Ca2+]i versus force plot tracked the common path in the rising and relaxation phases of K+ contractures. In the second series of experiments, 2,5-di-tert-butylhydroquinone (TBQ), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, was used to decrease the rate of decline of [Ca2+]i after tetanic stimulation. The decay time courses of both [Ca2+]i and force were dose-dependently slowed by TBQ up to 5 μM; the instantaneous [Ca2+]i– force relations were nearly identical at ≥1 μM TBQ, suggesting that the change in [Ca2+]i was slow enough to reach equilibrium with force. The [Ca2+]i–force data obtained from the two types of experiments were consistent with the Hill curve using a Hill coefficient of 3.2–3.9 and [Ca2+]i for half activation (Ca50) of 1.5–1.7 μM. However, if fura dextran reacts with Ca2+ with a 2.5-fold greater Kd as previously estimated from the kinetic fitting (Konishi and Watanabe. 1995. J. Gen. Physiol. 106:1123–1150), Ca50 would be 3.7–4.2 μM. We also studied the [Ca2+]–force relation in skinned fibers under similar experimental conditions. The average Hill coefficient and Ca50 were estimated to be 3.3 and 1.8 μM, respectively. Although uncertainties remain about the precise levels of [Ca2+]i, we conclude that the steady state force is a 3rd to 4th power function of [Ca2+]i, and Ca50 is in the low micromolar range in intact frog muscle fibers, which is in reasonable agreement with results obtained from skinned fibers.

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