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.

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.

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.

Effects of pH on the length-dependent twitch potentiation in skeletal muscle

2002 ◽  
Vol 92 (3) ◽  
pp. 1293-1299 ◽  
Author(s):  
Dilson E. Rassier ◽  
Walter Herzog
Keyword(s):  
Skeletal Muscle ◽  
Force Production ◽  
Optimal Length ◽  
Twitch Potentiation ◽  
Length Dependence ◽  
Charge Potential ◽  
Before And After ◽  
Effects Of Ph ◽  
Isometric Twitch

When muscle is elongated, there is a length dependence of twitch potentiation and an increased Ca2+ sensitivity of the myofilaments. Changes in the charge potential of myofilaments, induced by a decrease in pH, are known to abolish the length dependence of Ca2+ sensitivity. This study was aimed at testing the hypothesis that a decrease in pH, and the concomitant loss of length dependence of Ca2+sensitivity, depresses the length dependence of staircase potentiation. In vitro, isometric twitch contractions of fiber bundles dissected from the mouse extensor digitorum longus, performed before and after 10 s of 10-Hz stimulation (i.e., the staircase potentiation protocol) were analyzed at five different lengths, ranging from optimal length for maximal force production ( L o; = 12 ± 0.7 mm) to L o + 1.2 mm ( L o + 10%). These measurements were made at an extracellular pH of 6.6, 7.4, and 7.8 (pH changes induced by altering the CO2 concentration of the bath solution). At pH 7.4 and 7.8, the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased fiber bundle length ( r 2 = 0.95 and r 2 = 0.99, respectively). At pH 6.6, the length dependence of potentiation was abolished, and the slope of the length-potentiation relationship was not different from zero ( r 2 = 0.05). The results of this study indicate that length dependence of potentiation in intact skeletal muscle is abolished by lowering the pH. Because decreasing the pH decreases Ca2+ sensitivity and changes the charge potential of the filaments, the mechanism of length-dependent potentiation may be closely related to the length dependence of Ca2+sensitivity, and changes in the charge potential of the myofilaments may be important in regulating this relationship.

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.

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.

Endothelial modulation of skeletal muscle blood flow andV˙o 2 during low- and high-intensity contractions

2002 ◽  
Vol 92 (2) ◽  
pp. 461-468 ◽  
Author(s):  
Cheryl E. King-VanVlack ◽  
J. D. Mewburn ◽  
C. K. Chapler ◽  
P. H. MacDonald
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Methyl Ester ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Tension Development ◽  
Anesthetized Dogs ◽  
Isometric Twitch ◽  
Oxide Synthase

In the present study, we determined whether endothelin (ET)-1 contributed to the observed reduction in muscle blood flow (Q˙) during contractions with nitric oxide synthase (NOS) inhibition and whether muscle O2 uptake (V˙o 2) would be affected by the decrease in muscle Q˙ with NOS inhibition at different contraction intensities. Muscle Q˙,V˙o 2, O2 extraction ratio (OER), and tension development (TD) were studied in the in situ gastrocnemius muscle preparation in anesthetized dogs. A decrease in the V˙o 2-to-TD ratio (V˙o 2/TD) was used as an indicator of O2 limitation. Three contraction protocols were used: 1) isometric twitch contractions at 2 twitches (tw)/s, 2) the same contractions at 4 tw/s, and 3) pretreatment with an ETA-receptor antagonist (BQ-123) before 2 tw/s contractions. The muscle was stimulated to contract, and measures were obtained at steady state (∼5–8 min). NOS inhibition ( N ω-nitro-l-arginine methyl ester) was then induced, and measures were repeated at 2, 5, 10, and 15 min. During 2 tw/s contractions, NOS inhibition reduced Q˙with and without ETA-receptor blockade. In both groups, OER increased in response to the fall in Q˙, with the result being no change in V˙o 2/TD. NOS inhibition also decreased Q˙ during 4 tw/s contractions, but OER did not increase, resulting in a reduction inV˙o 2/TD 5 and 15 min after N ω-nitro-l-arginine methyl ester. These data indicated that 1) a reciprocal increase in ET-1 during NOS inhibition does not influence active hyperemia in skeletal muscle, and 2) during 4 tw/s contractions, the ischemia with NOS inhibition was associated with either an O2 limitation or an alteration in the efficiency of muscle contractions.

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.

Functional significance of compensatory overloaded rat fast muscle

1982 ◽  
Vol 52 (2) ◽  
pp. 473-478 ◽  
Author(s):  
R. R. Roy ◽  
I. D. Meadows ◽  
K. M. Baldwin ◽  
V. R. Edgerton
Keyword(s):  
Biochemical Properties ◽  
Slow Muscle ◽  
Repetitive Stimulation ◽  
Contractile Properties ◽  
Sectional Area ◽  
Shortening Velocity ◽  
Cross Sectional ◽  
Time To Peak ◽  
Isometric Twitch

Chronic overload of a skeletal muscle by removing its synergists produces hypertrophy and marked changes in its metabolic and biochemical properties. In this study alterations in the contractile properties of the plantaris 12–14 wk after bilateral removal of the soleus and gastrocnemius were investigated. In situ isometric and isotonic contractile properties of overloaded plantaris (OP), normal plantaris (NP), and normal soleus (NS) were tested at 33 +/- 1 degree C. Op were 97% heavier than NP and produced 43 and 46% higher twitch (Pt) and tetanic (Po) tensions. However, NP produced more tension per cross-sectional area than OP (mean 26.2 vs. 21.6 N/cm2; P less than 0.001). Isometric twitch time to peak tension (TPT) and half-relaxation time (1/2RT) were significantly longer in OP (mean 36.4 vs. 32.5 ms and 23.9 vs. 18.4 ms). Mean maximum shortening velocity (Vmax, mm/s per 1,000 sarcomeres) were 34.1 for NP and 18.1 for OP (P less than 0.001). The degree of conversion toward the Vmax of NS was 74% compared with only 19 and 14% for TPT and 1/2RT. OP produced a higher proportion of Po at a given stimulation frequency than NP and showed less fatigue than NP after repetitive stimulation. Chronic overload of the fast plantaris modified to varying degrees the contractile properties studied toward that resembling a slow muscle. Although the maximum tension of OP was markedly enhanced it was not in proportion to the increase in muscle mass.

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.

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