scholarly journals Phenol increases intracellular [Ca2+] during twitch contractions in intact Xenopus skeletal myofibers

2010 ◽  
Vol 109 (5) ◽  
pp. 1384-1393 ◽  
Author(s):  
Leonardo Nogueira ◽  
Michael C. Hogan
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Muscle Function ◽  
Ryanodine Receptors ◽  
Muscle Fibers ◽  
Muscle Contractility ◽  
Tension Development ◽  
Low Concentrations ◽  
Intact Muscle ◽  
Intracellular Ca

Phenol is a neurolytic agent used for management of spasticity in patients with either motoneuron lesions or stroke. In addition, compounds that enhance muscle contractility (i.e., polyphenols, etc.) may affect muscle function through the phenol group. However, the effects of phenol on muscle function are unknown, and it was, therefore, the purpose of the present investigation to examine the effects of phenol on tension development and Ca2+ release in intact skeletal muscle fibers. Dissected intact muscle fibers from Xenopus laevis were electrically stimulated, and cytosolic Ca2+ concentration ([Ca2+]c) and tension development were recorded. During single twitches and unfused tetani, phenol significantly increased [Ca2+]c and tension without affecting myofilament Ca2+ sensitivity. To investigate the phenol effects on Ca2+ channel/ryanodine receptors, single fibers were treated with different concentrations of caffeine in the presence and absence of phenol. Low concentrations of phenol significantly increased the caffeine sensitivity ( P < 0.01) and reduced the caffeine concentrations necessary to produce nonstimulated contraction (contracture). However, at high phenol concentrations, caffeine did not increase tension or Ca2+ release. These results suggest that phenol affects the ability of caffeine to release Ca2+ through an effect on the ryanodine receptors, or on the sarcoplasmic reticulum Ca2+ pump. During tetanic contractions inducing fatigue, phenol application decreased the time to fatigue. In summary, phenol increases intracellular [Ca2+] during twitch contractions in muscle fibers without altering myofilament Ca2+ sensitivity and may be used as a new agent to study skeletal muscle Ca2+ handling.

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.

Effect of β-adrenoceptor activation on [Ca2+]i regulation in murine skeletal myotubes

1999 ◽  
Vol 276 (5) ◽  
pp. C1038-C1045 ◽  
Author(s):  
Y. S. Prakash ◽  
H. F. M. van der Heijden ◽  
E. M. Gallant ◽  
G. C. Sieck
Keyword(s):  
Skeletal Muscle ◽  
Ryanodine Receptors ◽  
Immunocytochemical Staining ◽  
Skeletal Muscle Myosin ◽  
Low Concentrations ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Mouse Limb ◽  
High Concentrations ◽  
Muscle Myosin

The present study used real-time confocal microscopy to examine the effects of the β2-adrenoceptor agonist salbutamol on regulation of intracellular Ca2+ concentration ([Ca2+]i) in myotubes derived from neonatal mouse limb muscles. Immunocytochemical staining for ryanodine receptors and skeletal muscle myosin confirmed the presence of sarcomeres. The myotubes displayed both spontaneous and ACh-induced rapid (<2-ms rise time) [Ca2+]itransients. The [Ca2+]itransients were frequency modulated by both low and high concentrations of salbutamol. Exposure to α-bungarotoxin and tetrodotoxin inhibited ACh-induced [Ca2+]itransients and the response to low concentrations of salbutamol but not the response to higher concentrations. Preexposure to caffeine inhibited the subsequent [Ca2+]iresponse to lower concentrations of salbutamol and significantly blunted the response to higher concentrations. Preexposure to salbutamol diminished the [Ca2+]iresponse to caffeine. Inhibition of dihydropyridine-sensitive Ca2+ channels with nifedipine or PN-200-110 did not prevent [Ca2+]ielevations induced by higher concentrations of salbutamol. The effects of salbutamol were mimicked by the membrane-permeant analog dibutyryl adenosine 3′,5′-cyclic monophosphate. These data indicate that salbutamol effects in skeletal muscle predominantly involve enhanced sarcoplasmic reticulum Ca2+ release.

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.

Effect of indomethacin on force responses and sarcoplasmic reticulum function in skinned skeletal muscle fibers and cytosolic [Ca2+] in myotubes

2003 ◽  
Vol 285 (4) ◽  
pp. C881-C890 ◽  
Author(s):  
Renzhi Han ◽  
Takuya Suizu ◽  
Miranda D. Grounds ◽  
Anthony J. Bakker
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Aristolochic Acid ◽  
Muscle Fibers ◽  
Force Production ◽  
Contractile Apparatus ◽  
Intracellular Ca ◽  
Flexor Digitorum Brevis ◽  
Edl Muscle ◽  
Flexor Digitorum

In this study, the effects of phospholipase A2 (PLA2) inhibitors on excitation-contraction coupling (ECC) and sarcoplasmic reticulum (SR) function were examined in skinned extensor digitorum longus (EDL) muscle fibers of the rat. The nonspecific PLA2 inhibitor indomethacin (200 μM) significantly increased the peak (∼2-fold, P = 0.02) and the width (∼6-fold, P = 0.008) of depolarization-induced force responses (DIFRs) elicited in the fibers ( n = 4). Exposure of the skinned EDL fibers to indomethacin (200 μM) ( n = 7) and another PLA2 inhibitor quinacrine (200 μM) ( n = 5) resulted in the return of large DIFRs after use-dependent rundown. However, aristolochic acid (100 μM), an inhibitor of secretory PLA2, failed to return DIFRs after rundown. Indomethacin did not protect against the loss of DIFRs induced by exposure to elevated myofibrilar [Ca2+]. Indomethacin (200 μM) produced a small but significant increase in the Ca2+ sensitivity of the contractile apparatus of skinned EDL fibers and the maximum force production. Indomethacin (200 μM) also had significant effects on SR function, increasing SR Ca2+ loading in the skinned fibers (117.2 ± 3.0% of controls, P = 0.0008, n = 8) and inducing intracellular Ca2+ release in isolated intact flexor digitorum brevis (FDB) fibers ( n = 7) and C2C12 myotubes ( n = 6). These data suggest that intracellular PLA2 may be an important modulator of ECC in skeletal muscle.

Pharmacological evidence for two types of myocardial sarcoplasmic reticulum Ca2+ release

1991 ◽  
Vol 260 (3) ◽  
pp. H785-H795
Author(s):  
C. Lynch
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Local Anesthetics ◽  
Papillary Muscles ◽  
Initial Tension ◽  
Tension Development ◽  
Short Cycle ◽  
Peak Tension ◽  
Low Concentrations ◽  
Cycle Lengths ◽  
Initial Delay

Contractions of guinea pig papillary muscles were studied at 37 degrees C under a variety of conditions and stimulation rates that markedly alter the pattern of tension development. When rested-state contractions (RSCs) were enhanced by treatments that increase intracellular adenosine 3',5'-cyclic monophosphate (0.1-1 microM isoproterenol, 1-10 microM forskolin), a markedly enhanced late peak tension developed after a 100-ms delay. Such late peak tension was selectively depressed by local anesthetics (200-400 microM procaine, 4-10 microM tetracaine, or 0.5-1 mM ethyl aminobenzoate). In contrast, 0.1-1 microM ryanodine had little effect on late peak tension, whereas 5 mM caffeine reduced the delay before tension development. Inotropic interventions such as increased external Ca2+ concentration or the Ca2+ channel agonist BAY K 8644 did not elicit such distinct late peaking RSCs. Rapid initial tension development observed under a variety of situations (short cycle lengths, stimulation rates of 0.25 Hz plus isoproterenol, decreased external Na+ concentration) was markedly depressed by 0.01-1 microM ryanodine and by caffeine, whereas local anesthetics had little effect. These results suggest two pharmacologically distinct types of sarcoplasmic reticulum Ca2+ release: 1) Ca2+ that accumulates during prior depolarizations is released immediately upon depolarization and decreased by ryanodine and caffeine; 2) extracellular Ca2+ that enters the myocyte is accumulated and released after an initial delay and is selectively depressed by low concentrations of local anesthetics.

Characterization of RyR1-slow, a ryanodine receptor specific to slow-twitch skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. R1889-R1898 ◽  
Author(s):  
Jeffery Morrissette ◽  
Le Xu ◽  
Alexandra Nelson ◽  
Gerhard Meissner ◽  
Barbara A. Block
Keyword(s):  
Skeletal Muscle ◽  
Single Channel ◽  
Fiber Type ◽  
Ryanodine Receptors ◽  
Open Probability ◽  
Dependent Inhibition ◽  
Single Channel Activity ◽  
Intracellular Ca ◽  
Slow Twitch ◽  
Fast Twitch

Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type–specific manner in fish skeletal muscle (11). In this study, we compare [3H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [3H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (Po) of RyR1-slow was threefold less than the maximum Po of RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest Po of all the RyR channels and displayed less inhibition at millimolar Ca2+. The addition of 5 mM Mg-ATP or 2.5 mM β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP) to the channels increased the Po and [3H]ryanodine binding of both RyR1s but also caused a shift in the Ca2+ dependency curve of RyR1-slow such that Ca2+-dependent inactivation was attenuated. [3H]ryanodine binding data also showed that Mg2+-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca2+ is regulated in these muscle types.

Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum

1997 ◽  
Vol 82 (2) ◽  
pp. 447-452 ◽  
Author(s):  
Terence G. Favero ◽  
, Anthony C. Zable ◽  
, David Colter ◽  
Jonathan J. Abramson
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Single Channel ◽  
Channel Activity ◽  
Release Channel ◽  
Muscle Lactate ◽  
Tension Development ◽  
Contraction Coupling ◽  
Single Channel Activity ◽  
High Concentrations

Favero, Terence G., Anthony C. Zable, David Colter, and Jonathan J. Abramson. Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum. J. Appl. Physiol. 82(2): 447–452, 1997.—Sarcoplasmic reticulum (SR) Ca2+-release channel function is modified by ligands that are generated during about of exercise. We have examined the effects of lactate on Ca2+- and caffeine-stimulated Ca2+ release, [3H]ryanodine binding, and single Ca2+-release channel activity of SR isolated from rabbit white skeletal muscle. Lactate, at concentrations from 10 to 30 mM, inhibited Ca2+- and caffeine-stimulated [3H]ryanodine binding to and inhibited Ca2+- and caffeine-stimulated Ca2+ release from SR vesicles. Lactate also inhibited caffeine activation of single-channel activity in bilayer reconstitution experiments. These findings suggest that intense muscle activity, which generates high concentrations of lactate, will disrupt excitation-contraction coupling. This may lead to decreases in Ca2+ transients promoting a decline in tension development and contribute to muscle fatigue.

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