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

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.

2000 ◽  
Vol 78 (4) ◽  
pp. 350-357 ◽  
Author(s):  
Dilson E Rassier ◽  
Brian R MacIntosh

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.


2002 ◽  
Vol 92 (3) ◽  
pp. 1293-1299 ◽  
Author(s):  
Dilson E. Rassier ◽  
Walter Herzog

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.


1997 ◽  
Vol 273 (1) ◽  
pp. C198-C204 ◽  
Author(s):  
D. E. Rassier ◽  
L. A. Tubman ◽  
B. R. MacIntosh

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.


1979 ◽  
Vol 237 (1) ◽  
pp. C38-C42 ◽  
Author(s):  
C. R. Lambert ◽  
L. B. Gladden ◽  
W. N. Stainsby

This study was designed to assess the contribution of length-dependent activation to the peak isometric twitch tension developed and the maximal rate of tension development (dP/dt) of in situ canine skeletal muscle. Length-developed tension and length-dP/dt relationships were generated for the dog gastrocnemius-plantaris muscle group at three different levels of inotropic state as determined by stimulation frequency. These relationships were then normalized with respect to maximal developed tension and maximal dP/dt and the normalized curves were superimposed for comparison. At progressively shorter muscle lengths the augmentation of tension production by a given increment in inotropic state was greater as measured by either developed tension or dP/dt. Thus, a given change in muscle length produced a greater change in performance in less potentiated muscles. These findings are similar to those from studies of isolated cardiac muscle and illustrate the lack of independence between activational state and muscle length for in situ skeletal muscle.


2004 ◽  
Vol 97 (2) ◽  
pp. 764-772 ◽  
Author(s):  
Jefferson C. Frisbee

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.


1998 ◽  
Vol 275 (6) ◽  
pp. L1026-L1030 ◽  
Author(s):  
Martin Bard ◽  
Sergio Salmeron ◽  
Catherine Coirault ◽  
Francois-Xavier Blanc ◽  
Yves Lecarpentier

In the guinea pig, tracheal smooth muscle (TSM) exhibits intrinsic tone (IT). The active nature of IT suggests that it could be influenced by muscle length and load. In the guinea pig, IT is entirely suppressed by the cyclooxygenase inhibitor indomethacin. IT could be measured as the difference between resting tone before and after indomethacin addition. We examined, in electrically stimulated TSM strips ( n= 9), the influence of initial muscle length ( L i) on IT, the relationship between IT and the maximum extent of relaxation (ΔF1), and the influence of indomethacin on active isometric force. When L i decreased from 100 to 75% of optimal L i, there was a significant decrease in IT (from 12.0 ± 0.2 to 5.3 ± 0.1 mN; P < 0.001). Over the range of L i studied, ΔF1 underestimated the amount of IT, but there was a close linear relationship between ΔF1 and IT ( r = 0.9). Compared with the basal state, indomethacin increased active isometric force (from 9.5 ± 1.0 to 19.7 ± 2.0 mN at optimal L i; P < 0.001) and induced its length dependency. In guinea pig TSM, L i was an important determinant of IT.


1999 ◽  
Vol 277 (5) ◽  
pp. L968-L974 ◽  
Author(s):  
Steven S. An ◽  
Chi-Ming Hai

Mechanical strain regulates the maximal level of myosin light chain phosphorylation mediated by muscarinic activation in airway smooth muscle. Accordingly, we tested the hypothesis that mechanical strain regulates maximal phosphatidylinositol (PI) turnover ( V max) coupled to muscarinic receptors in bovine tracheal smooth muscle. We found that PI turnover was not significantly length dependent in unstimulated tissues. However, carbachol-induced PI turnover was linearly dependent on muscle length at both 1 and 100 μM. The observed linear length dependence of PI turnover at maximal carbachol concentration (100 μM) suggests that mechanical strain regulates V max. When carbachol concentration-PI turnover relationships were measured at optimal length and at 20% optimal length, the results could be explained by changes in V max alone. To determine whether the length-dependent step is upstream from heterotrimeric G proteins, we investigated the length dependence of fluoroaluminate-induced PI turnover. The results indicate that fluoroaluminate-induced PI turnover remained significantly length dependent at maximal concentration. These findings together suggest that regulating functional units of G proteins and/or phospholipase C enzymes may be the primary mechanism of mechanosensitive modulation in airway smooth muscle.


1988 ◽  
Vol 66 (6) ◽  
pp. 829-832 ◽  
Author(s):  
Claude Côté ◽  
Timothy P. White ◽  
John A. Faulkner

We investigated the relationship between oxidative capacity, substrate depletion, and fatigability of muscle grafts in situ. Isometric contractile properties and fatigability were measured in stabilized grafts and control muscles from age-matched rats. Intramuscular glycogen and triglyceride concentrations were measured before and after the fatigue protocol. Even though stabilized soleus grafts have a reduced oxidative capacity compared with control soleus muscles, no difference was observed between groups in terms of resistance to fatigue. Glycogen concentrations did not decrease significantly during the fatigue protocol in either group. Compared with control muscles, the triglyceride concentration in the grafts was significantly higher before the fatigue protocol and it decreased significantly more following the fatigue protocol.


2004 ◽  
Vol 97 (4) ◽  
pp. 1195-1202 ◽  
Author(s):  
S. Parikh ◽  
D. L. Morgan ◽  
J. E. Gregory ◽  
U. Proske

Subjecting a muscle to a series of eccentric contractions in which the contracting muscle is lengthened results in a number of changes in its mechanical properties. These include a fall in isometric tension that is particularly pronounced during low-frequency stimulation, a phenomenon known as low-frequency depression (LFD). Reports of LFD have not taken into account the shift in optimum length for active tension generation to longer muscle lengths that takes place after eccentric contractions. Given the length dependence of the stimulation frequency-tension curve, we tested the hypothesis that the change in this relationship after eccentric exercise is due to the shift in optimum length. We measured LFD by recording tension in response to a linearly increasing rate of stimulation of the nerve to medial gastrocnemius of anesthetized cats, over the range 0–100 pulses per second. Tension responses were measured before and after 50 eccentric contractions consisting of 6-mm stretches starting at 3 mm below optimum length and finishing at 3 mm above it. An index of LFD was derived from the tension responses to ramp stimulation. It was found that LFD after the eccentric contractions was partly, but not entirely, due to changes in the muscle's optimum length. An additional factor was the effect of fatigue. These observations led to the conclusion that the muscle length dependence of LFD was reduced by eccentric contractions. All of this means that after eccentric exercise the tension deficit at low rates of muscle activation is likely to be less severe than first thought.


1992 ◽  
Vol 73 (5) ◽  
pp. 2105-2111 ◽  
Author(s):  
B. T. Ameredes ◽  
W. F. Brechue ◽  
G. M. Andrew ◽  
W. N. Stainsby

The force-velocity (F-V) relationships of canine gastrocnemius-plantaris muscles at optimal muscle length in situ were studied before and after 10 min of repetitive isometric or isotonic tetanic contractions induced by electrical stimulation of the sciatic nerve (200-ms trains, 50 impulses/s, 1 contraction/s). F-V relationships and maximal velocity of shortening (Vmax) were determined by curve fitting with the Hill equation. Mean Vmax before fatigue was 3.8 +/- 0.2 (SE) average fiber lengths/s; mean maximal isometric tension (Po) was 508 +/- 15 g/g. With a significant decrease of force development during isometric contractions (-27 +/- 4%, P < 0.01, n = 5), Vmax was unchanged. However, with repetitive isotonic contractions at a low load (P/Po = 0.25, n = 5), a significant decrease in Vmax was observed (-21 +/- 2%, P < 0.01), whereas Po was unchanged. Isotonic contractions at an intermediate load (P/Po = 0.5, n = 4) resulted in significant decreases in both Vmax (-26 +/- 6%, P < 0.05) and Po (-12 +/- 2%, P < 0.01). These results show that repeated contractions of canine skeletal muscle produce specific changes in the F-V relationship that are dependent on the type of contractions being performed and indicate that decreases in other contractile properties, such as velocity development and shortening, can occur independently of changes in isometric tension.


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