Length-dependent potentiation and myosin light chain phosphorylation in rat gastrocnemius muscle

1997 ◽  
Vol 273 (1) ◽  
pp. C198-C204 ◽  
Author(s):  
D. E. Rassier ◽  
L. A. Tubman ◽  
B. R. MacIntosh
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Average Rate ◽  
Muscle Length ◽  
Repetitive Stimulation ◽  
Mammalian Skeletal Muscle ◽  
Optimal Length ◽  
Regulatory Light Chains ◽  
Dependent Change

Changes in muscle length affect the degree of staircase potentiation in skeletal muscle, but the mechanism by which this occurs is unknown. In this study, we tested the hypothesis that length-dependent change in staircase is modulated by phosphorylation of the myosin regulatory light chains (RLC), since this is believed to be the main mechanism of potentiation. In situ isometric contractile responses of rat gastrocnemius muscle during 10 s of repetitive stimulation at 10 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. The degree of enhancement of developed tension during 10 s of repetitive stimulation was observed to be length dependent, with increases of 118.5 +/- 7.8, 63.1 +/- 3.9, and 45.6 +/- 4.1% (means +/- SE) at Lo - 10%, Lo, and Lo + 10%, respectively. Staircase was accompanied by increases in the average rate of force development of 105.6 +/- 7.7, 55.6 +/- 4.1, and 37.2 +/- 4.4% for Lo - 10%, Lo, and Lo + 10%, respectively. RLC phosphorylation after 10 s of 10-Hz stimulation was higher than under resting conditions but not different among Lo - 10% (40 +/- 3.5%), Lo (35 +/- 3.5%), and Lo + 10% (41 +/- 3.5%). This study shows that there is a length dependence of staircase potentiation in mammalian skeletal muscle that may not be directly modulated by RLC phosphorylation. Interaction of RLC phosphorylation with length-dependent changes in Ca2+ release and intermyofilament spacing may explain these observations.

Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium

2000 ◽  
Vol 78 (4) ◽  
pp. 350-357 ◽  
Author(s):  
Dilson E Rassier ◽  
Brian R MacIntosh
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Repetitive Stimulation ◽  
Mammalian Skeletal Muscle ◽  
Optimal Length ◽  
Dantrolene Sodium ◽  
Length Dependence ◽  
Before And After ◽  
Isometric Twitch

In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 ± 12, 51 ± 5, and 34 ± 9% (mean ± SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65±13, 53 ± 11, and 45 ± 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 ± 17, 26 ± 8, and 18 ± 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

Caffeine and length dependence of staircase potentiation in skeletal muscle

1998 ◽  
Vol 76 (10-11) ◽  
pp. 975-982 ◽  
Author(s):  
Dilson E Rassier ◽  
L Aaron Tubman ◽  
Brian R MacIntosh
Keyword(s):  
Skeletal Muscle ◽  
Muscle Length ◽  
Negative Slope ◽  
Muscle Twitch ◽  
Optimal Length ◽  
Length Dependence ◽  
Before And After ◽  
Isometric Twitch ◽  
The Relationship

Skeletal muscle sensitivity to Ca2+ is greater at long lengths, and this results in an optimal length for twitch contractions that is longer than optimal length for tetanic contractions. Caffeine abolishes this length dependence of Ca2+ sensitivity. Muscle length (ML) also affects the degree of staircase potentiation. Since staircase potentiation is apparently caused by an increased Ca2+ sensitivity of the myofilaments, we tested the hypothesis that caffeine depresses the length dependence of staircase potentiation. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 10 s of 10-Hz stimulation were analyzed at seven different lengths to evaluate the length dependence of staircase potentiation. In the absence of caffeine, length dependence of Ca2+ sensitivity was observed, and the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased length (DT = 1.47 - 0.05ML, r2 = 0.95, where DT is developed tension). Length dependence of Ca2+ sensitivity was decreased by caffeine when caffeine was administered in amounts estimated to result in 0.5 and 0.75 mM concentrations. Furthermore, the negative slope of the relationship between staircase potentiation and muscle length was diminished at the lower caffeine dose, and the slope was not different from zero after the higher dose (DT = 1.53 - 0.009ML, r2 = 0.43). Our study shows that length dependence of Ca2+ sensitivity in intact skeletal muscle is diminished by caffeine. Caffeine also suppressed the length dependence of staircase potentiation, suggesting that the mechanism of this length dependence may be closely related to the mechanism for length dependence of Ca2+ sensitivity.Key words: skeletal muscle, twitch contraction, Ca2+ sensitivity, muscle length, staircase.

An integrative, in situ approach to examining K+ flux in resting skeletal muscle

2001 ◽  
Vol 79 (12) ◽  
pp. 996-1006 ◽  
Author(s):  
Michael I Lindinger ◽  
Thomas J Hawke ◽  
Lisa Vickery ◽  
Laurie Bradford ◽  
Shonda L Lipskie
Keyword(s):  
Skeletal Muscle ◽  
Drug Effects ◽  
Potassium Transport ◽  
Mammalian Skeletal Muscle ◽  
Minimal Effect ◽  
Bovine Erythrocyte ◽  
Perfusion Medium ◽  
Sodium Potassium ◽  
Unidirectional Flux

The contributions of Na+/K+-ATPase, K+ channels, and the NaK2Cl cotransporter (NKCC) to total and unidirectional K+ flux were determined in mammalian skeletal muscle at rest. Rat hindlimbs were perfused in situ via the femoral artery with a bovine erythrocyte perfusion medium that contained either 86Rb or 42K, or both simultaneously, to determine differences in ability to trace unidirectional K+ flux in the absence and presence of K+-flux inhibitors. In most experiments, the unidirectional flux of K+ into skeletal muscle (JinK) measured using 86Rb was 8–10% lower than JinK measured using 42K. Ouabain (5 mM) was used to inhibit Na+/K+-ATPase activity, 0.06 mM bumetanide to inhibit NKCC activity, 1 mM tetracaine or 0.5 mM barium to block K+ channels, and 0.05 mM glybenclamide (GLY) to block ATP-sensitive K+ (KATP) channels. In controls, JinK remained unchanged at 0.31 ± 0.03 µmol·g–1·min–1 during 55 min of perfusion. The ouabain-sensitive Na+/K+-ATPase contributed to 50 ± 2% of basal JinK, K+ channels to 47 ± 2%, and the NKCC to 12 ± 1%. GLY had minimal effect on JinK, and both GLY and barium inhibited unidirectional efflux of K+ (JoutK) from the cell through K+ channels. Combined ouabain and tetracaine reduced JinK by 55 ± 2%, while the combination of ouabain, tetracaine, and bumetanide reduced JinK by 67 ± 2%, suggesting that other K+-flux pathways may be recruited because the combined drug effects on inhibiting JinK were not additive. The main conclusions are that the NKCC accounted for about 12% of JinK, and that KATP channels accounted for nearly all of the JoutK, in resting skeletal muscle in situ.Key words: sodium potassium chloride cotransporter, NKCC, Na+/K+-ATPase, potassium channels, potassium transport, in situ rat hindlimb.

Enhanced arteriolar α-adrenergic constriction impairs dilator responses and skeletal muscle perfusion in obese Zucker rats

2004 ◽  
Vol 97 (2) ◽  
pp. 764-772 ◽  
Author(s):  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Zucker Rats ◽  
Metabolic Demand ◽  
Obese Zucker Rats ◽  
Isometric Twitch ◽  
Gastrocnemius Muscles

The present study tested the hypothesis that enhanced vascular α-adrenergic constriction in obese Zucker rats (OZR) impairs arteriolar dilation and perfusion of skeletal muscle at rest and with increased metabolic demand. In lean Zucker rats (LZR) and OZR, isolated gracilis arterioles were viewed via television microscopy, and the contralateral cremaster muscle or gastrocnemius muscle was prepared for study in situ. Gracilis and cremasteric arterioles were challenged with dilator stimuli under control conditions and after blockade of α-adrenoreceptors with prazosin, phentolamine, or yohimbine. Gastrocnemius muscles performed isometric twitch contractions of increasing frequency, and perfusion was continuously monitored. In OZR, dilator responses of arterioles to hypoxia (gracilis), wall shear rate (cremaster), acetylcholine, and iloprost (both) were impaired vs. LZR. Treatment with prazosin and phentolamine (and in cremasteric arterioles only, yohimbine) improved arteriolar reactivity to these stimuli in OZR, although responses remained impaired vs. LZR. Gastrocnemius muscle blood flow was reduced at rest in OZR; this was corrected with intravenous infusion of phentolamine or prazosin. At all contraction frequencies, blood flow was reduced in OZR vs. LZR; this was improved by infusion of phentolamine or prazosin at low-moderate metabolic demand only (1 and 3 Hz). At 5 Hz, adrenoreceptor blockade did not alter blood flow in OZR from levels in untreated rats. These results suggest that enhanced α-adrenergic constriction of arterioles of OZR contributes to impaired dilator responses and reduced muscle blood flow at rest and with mild-moderate (although not with large) elevations in metabolic demand.

Effect of initial length on relations between oxygen uptake and load in dog muscle

1976 ◽  
Vol 230 (4) ◽  
pp. 1008-1012 ◽  
Author(s):  
WN Stainsby ◽  
JK Barclay
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Uptake ◽  
The Other ◽  
Mammalian Skeletal Muscle ◽  
Initial Length ◽  
Muscle Preparation ◽  
Optimal Length ◽  
Muscle Energetics ◽  
Isotonic Contractions ◽  
Fenn Effect

Oxygen uptake for brief tetanic contractions was calculated from measurements of blood flow and blood arteriovenous oxygen content differences. Each muscle preparation was pretested under isometric conditions to establish optimal length, Lo. After this one group of preparations performed afterload isotonic contractions at several loads with initial length, Li, less than Lo. The other groups of preparations performed similar contractions with Li greater than Lo. When Li was less than Lo, oxygen uptake for the highest load was always greater than oxygen uptake at the lowest load whereas intermediate loads were usually higher than both extremes. However, when Li was greater than Lo, oxygen uptake at the highest load was always less than oxygen uptake at the lowest load; again the intermediate loads were usually higher than both extremes. The data confirm and extend similar effects of initial length on heat production for contractions by amphibian muscles (7). It seems likely that the differences in initial lengths may account for the fact that the Fenn effect has not previously been observed in studies of mammalian skeletal muscle energetics.

Absence of staircase following disuse in rat gastrocnemius muscle

1988 ◽  
Vol 66 (6) ◽  
pp. 707-713 ◽  
Author(s):  
Brian R. MacIntosh ◽  
Marie-Cristine Roberge ◽  
Phillip F. Gardiner
Keyword(s):  
Skeletal Muscles ◽  
Time Course ◽  
Gastrocnemius Muscle ◽  
Repetitive Stimulation ◽  
Muscle Weight ◽  
Twitch Contraction ◽  
Fast Twitch ◽  
Pulse Stimulation ◽  
Stimulation Of

Repetitive stimulation of mammalian fast-twitch skeletal muscles will normally result in a positive staircase response. This phenomenon was investigated in the rat gastrocnemius muscle following a 2-week period of tetrodotoxin-induced disuse. Muscle inactivity was imposed by superfusing tetrodotoxin in saline over the left sciatic nerve via an implanted osmotic pump. In situ isometric contractile responses to double pulse stimulation and repetitive stimulation at 10 Hz were determined the day after removal of the pump. Two weeks of disuse resulted in 40% muscle weight loss. A twitch contraction gave the same force when expressed per gram of wet muscle weight in control muscles, 317 ± 24.6 [Formula: see text] g/g, as compared with tetrodotoxin-treated muscles, 328 ± 24.2 g/g. Both contraction time and half-relaxation time were prolonged following treatment with tetrodotoxin. Repetitive stimulation at 10 Hz resulted in a positive staircase response in the control muscles, but not in muscles of the tetrodotoxin-treated rats. The observed changes in the time course of the twitch contraction with repetitive stimulation following tetrodotoxin-induced disuse are consistent with alterations in sarcoplasmic reticulum handling of calcium. It is not certain if there is a change following disuse in the mechanism normally associated with staircase or if this mechanism is merely opposed by an early fatigue.

scholarly journals Nonuniform effects of endurance exercise training on vasodilation in rat skeletal muscle

2005 ◽  
Vol 98 (2) ◽  
pp. 753-761 ◽  
Author(s):  
R. M. McAllister ◽  
J. L. Jasperse ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Second Order ◽  
Skeletal Muscle Blood Flow ◽  
Endurance Exercise Training

Endurance exercise training (Ex) has been shown to increase maximal skeletal muscle blood flow. The purpose of this study was to test the hypothesis that increased endothelium-dependent vasodilation is associated with the Ex-induced increase in muscle blood flow. Furthermore, we hypothesized that enhanced endothelium-dependent dilation is confined to vessels in high-oxidative muscles that are recruited during Ex. To test these hypotheses, sedentary (Sed) and rats that underwent Ex (30 m/min × 10% grade, 60 min/day, 5 days/wk, 8–12 wk) were studied using three experimental approaches. Training effectiveness was evidenced by increased citrate synthase activity in soleus and vastus lateralis (red section) muscles ( P < 0.05). Vasodilatory responses to the endothelium-dependent agent acetylcholine (ACh) in situ tended to be augmented by training in the red section of gastrocnemius muscle (RG; Sed: control, 0.69 ± 0.12; ACh, 1.25 ± 0.15; Ex: control, 0.86 ± 0.17; ACh, 1.76 ± 0.27 ml·min−1·100 g−1·mmHg−1; 0.05 < P < 0.10 for Ex vs. Sed during ACh). Responses to ACh in situ did not differ between Sed and Ex for either the soleus muscle or white section of gastrocnemius muscle (WG). Dilatory responses of second-order arterioles from the RG in vitro to flow (4–8 μl/min) and sodium nitroprusside (SNP; 10−7 through10−4 M), but not ACh, were augmented in Ex (vs. Sed; P < 0.05). Dilatory responses to ACh, flow, and SNP of arterioles from soleus and WG muscles did not differ between Sed and Ex. Content of the endothelial isoform of nitric oxide synthase (eNOS) was increased in second-order, fourth-order, and fifth-order arterioles from the RG of Ex; eNOS content was similar between Sed and Ex in vessels from the soleus and WG muscles. These findings indicate that Ex induces endothelial adaptations in fast-twitch, oxidative, glycolytic skeletal muscle. These adaptations may contribute to enhanced skeletal muscle blood flow in endurance-trained individuals.

Ouabain stimulates unidirectional and net potassium efflux in resting mammalian skeletal muscle

2001 ◽  
Vol 79 (11) ◽  
pp. 932-941 ◽  
Author(s):  
Thomas J Hawke ◽  
Sarah Lessard ◽  
Lisa Vickery ◽  
Shonda L Lipskie ◽  
Michael I Lindinger
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Skeletal Muscle ◽  
Potassium Efflux ◽  
Hindlimb Muscle ◽  
Flexor Digitorum Brevis ◽  
Baseline Values ◽  
Flexor Digitorum ◽  
Subsequent Addition

The present study compared ouabain-sensitive unidirectional K+ flux into (JinK) and out of (JoutK) perfused rat hindlimb skeletal muscle in situ and mouse flexor digitorum brevis (FDB) in vitro. In situ, 5 mM ouabain inhibited 54 ± 4% of the total JinK in 28 ± 1 min, and increased the net and unidirectional efflux of K+ within 4 min. In contrast, 1.8 mM ouabain inhibited 40 ± 8% of the total JinK in 38 ± 2 min, but did not significantly affect JoutK. In vitro, 1.8 and 0.2 mM ouabain decreased JinK to a greater extent (83 ± 5%) than in situ, but did not significantly affect 42K loss rate compared with controls. The increase in unidirectional K+ efflux (JoutK) with 5 mM ouabain in situ was attributed to increased K+ efflux through cation channels, since addition of barium (1 mM) to ouabain-perfused muscles returned JoutK to baseline values within 12 min. Perfusion with 5 mM ouabain plus 2 mM tetracaine for 30 min decreased JinK 46 ± 9% (0.30 ± 0.03 to 0.16 ± 0.02 µmol·min–1·g–1), however tetracaine was unable to abolish the ouabain-induced increase in unidirectional K+ efflux. In both rat hindlimb and mouse FDB, tetracaine had no effect on JoutK. Perfusion of hindlimb muscle with 0.1 mM tetrodotoxin (TTX, a Na+ channel blocker) decreased JinK by 15 ± 1%, but had no effect on JoutK; subsequent addition of ouabain (5 mM) decreased JinK a further 32 ± 2%. The ouabain-induced increase in unidirectional K+ efflux did not occur when TTX was perfused prior to and during perfusion with 5 mM ouabain. We conclude that 5 mM ouabain increases the unidirectional efflux of K+ from skeletal muscle through a barium and TTX-sensitive pathway, suggestive of voltage sensitive Na+ channels, in addition to inhibiting Na+/K+-ATPase activity.Key words: cardiac glycoside, Na,K pump, K+ channels, Na+ channels, perfused rat hindlimb, flexor digitorum brevis, TTX, barium, tetracaine.

Posttetanic potentiation and skeletal muscle fatigue: interactions with caffeine

1987 ◽  
Vol 65 (2) ◽  
pp. 260-268 ◽  
Author(s):  
Brian R. MacIntosh ◽  
Philip F. Gardiner
Keyword(s):  
Gastrocnemius Muscle ◽  
Additive Group ◽  
Repetitive Stimulation ◽  
Posttetanic Potentiation ◽  
Contraction Time ◽  
Twitch Response ◽  
Fatigued Muscle ◽  
Proportional Change ◽  
Before And After

The purpose of this study was to determine the interaction of three factors that modify twitch contraction amplitude in the rat gastrocnemius muscle in situ: posttetanic potentiation, fatigue, and caffeine. Posttetanic (200 Hz for 1 s) twitch responses were observed before and after 15 Hz stimulation for 6 min (group FS), injection of caffeine (75 mg/kg dissolved in saline, gropu NC), a combination of both repetitive stimulation and caffeine injection (group FC), or no treatment (group NS). Developed tension increased significantly with posttetanic potentiation and caffeine injection and these potentiating factors were additive (group NC). Repetitive stimulation attenuated the twitch response and the fatigued muscle was still responsive to the potentiating factors. Posttetanic potentiation was accomplished primarily by a significant increase in the peak rate of force development whereas caffeine potentiation and fatigue were effected with a proportional change in contraction time. It seems likely that the mechanism of posttetanic potentiation is not the same as the mechanism of caffeine-induced potentiation. Caffeine-induced potentiation is known to be related to increased release of calcium. Because changes in contraction time with fatigue were opposite to those associated with caffeine potentiation, it is proposed that the attenuated twitch response in fatigue results from reduced release of calcium.

Insulin-induced hyperpolarization in mammalian skeletal muscle

1989 ◽  
Vol 256 (2) ◽  
pp. C368-C374 ◽  
Author(s):  
S. T. Iannaccone ◽  
K. X. Li ◽  
N. Sperelakis ◽  
D. A. Lathrop
Keyword(s):  
Skeletal Muscle ◽  
New York ◽  
Molecular Basis ◽  
Insulin Action ◽  
Normal Group ◽  
Mammalian Skeletal Muscle ◽  
Rat Skeletal Muscle ◽  
Normal Rat ◽  
Endogenous Release

Insulin-induced hyperpolarization of up to 9 mV has been described in isolated frog [J. Physiol. Lond. 252: 43-58, 1975; Am. J. Physiol. 251 (Cell Physiol. 4): C249-C254, 1979] and mammalian (Molecular Basis of Insulin Action, New York: Plenum, 1985, p. 451-463; Am. J. Physiol. 197: 524-526, 1959; Am. J. Physiol. 198: 1066-1070, 1960) skeletal muscle. We have shown that a similar hyperpolarization occurs in situ after administration of insulin in anesthetized rats. In streptozotocin (STZ)-treated rats, insulin produced approximately 66-70% of the hyperpolarization observed in normal rat skeletal muscle in situ. Administration of ouabain in situ blocked the insulin-induced hyperpolarization in the normal group of rats and significantly blunted the effect in the STZ group. These results suggest that insulin-induced hyperpolarization in skeletal muscle results from direct activation of the Na+-K+-ATPase pump. In isolated skeletal muscle from normal and STZ rats, there was no difference in the amount of the insulin-induced hyperpolarization. There was an additive, but small, hyperpolarizing effect of insulin and isoproterenol when administered in combination, suggesting that the greater magnitude of the insulin-induced hyperpolarization observed in situ in normal rats may be due to an additive effect of injected insulin and endogenous release of epinephrine. Alternatively, STZ treatment may directly alter the Na+-K+ pump so that its response to insulin is lessened.

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