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Biomedical subjects

J C Rüegg

Publications and source records attributed to J C Rüegg.

At least 127 records · Page 7Linked to original sources
PubMed1982

Decrease in stiffness during shortening in calcium activated skinned muscle fibers.

Single fibers from frog sartorius or semitendinosus muscle were mechanically skinned and activated in ATP salt solution containing 10 micro M Ca2+ (7 degrees C). After development of an isometric contraction, fibers were released at constant speed (0.03-2.4 s-1). During ramp shortening, stiffness was determined from the slope of the tension-length diagram obtained during superimposed quick stretches. Both force and stiffness decreased, as the ramp shortening proceeded and approached a steady value after about 60 ms. An increase in speed of shortening caused a decrease in fiber tension and stiffness and an increase in the ratio of stiffness to tension, suggesting a decrease in both the number of attached crossbridges and in the average force per crossbridge.

Animals↗
PubMed1982

Length dependence of calcium activated isometric force and immediate stiffness in living and glycerol extracted vascular smooth muscle.

Vascular smooth muscle series elasticity was examined in living and glycerinated preparations as a function of the tissue length or calcium elicited force. Isometrically contracted smooth muscle strips were submitted to small quick stretches and releases (rise time 1.5 ms). The resulting immediate tension changes were proportion to the length changes for length steps ranging from -0.5% L0 to +2% L0. Plotting the immediate tension changes versus the length steps resulted in force-extension diagrams of the series elasticity (T1-curves). The linear parts of the T1-curves extrapolated to a common abscissa intercept of about -1% to -2% L0 irrespective of the tissue length or the degree of calcium activated force. The slopes of the T1-curves taken as the stiffness of the series elasticity increased in proportion to the isometric tension and depended on the tissue length or the degree of calcium activation in a similar way as tension. It is concluded that tension changes due to changes in the calcium concentration or the tissue length are caused by a change in the number of attached crossbridges. Results obtained in "skinned" fibres were similar to the one obtained in living fibres indicating that electromechanical coupling was not a major factor in determining the decrease in isometric tension and stiffness at short lengths.

Adenosine Triphosphate↗
PubMed1982

Vascular smooth muscle. Calmodulin and cyclic AMP-dependent protein kinase after calcium sensitivity in porcine carotid skinned fibers.

Recent work on vascular smooth muscle actomyosin has indicated that the Ca2+ sensitivity of both ATPase and superprecipitation are affected by calmodulin (CaM) and cyclic AMP-dependent protein kinase (cPK). Using a "chemically skinned" arterial preparation, we have extended these observations to the intact structured contractile system. Media from hog carotid artery were skinned with 1% Triton X-100 followed by a 50% glycerol-ATP salt solution, in which the strips were stored at -25 degrees C. Small strips (thickness between 0.1 and 0.2 mm) were mounted isometrically and relaxed in a Mg-ATP salt solution, pH 6.7, Ca2+ 10(-8) M, 30 degrees C. Ca2+ elicited a contraction with an ED50 of 10(-6) M. Isometric force was between 1 and 4 mN, consistent with the force observed before skinning. With time, the preparation became less sensitive with an increase in ED50 to 10(-5.7) M. CaM (4 micro M) reverses this loss, stabilizes the preparation, and sharply accelerates the rate of tension development. The ED50 in the presence of 4 micro M CaM shifts to about 10(-7) M. This effect is dose-dependent, with the half maximal effect at about 0.4 micro M CaM. Submaximal Ca2+ contractions can be reversibly depressed by preincubation of relaxed fibers with cPK catalytic subunit (300 U/ml), even in the presence of 4 micro M CaM. An inhibition of about 50% of the contraction at 0.2 micro M Ca2+ was obtained, whereas only 20% inhibition was found at 6 micro M Ca2+. Our findings suggest that changes in vascular contractility cannot be described solely in terms of changes in cytoplasmic Ca2+, and that changes in the sensitivity of the contractile protein to a given Ca2+ concentration are also potential mechanisms for vasodilation.

Animals↗
PubMed1982

Stimulation of Ca++ binding and ATPase activity of dog cardiac myofibrils by AR-L 115BS, a novel cardiotonic agent.

AR-L 115BS, a benzimidazole derivative, is a positive inotropic agent that has been shown to increase active tension development and unloaded shortening velocity of chemically skinned heart muscle preparations at submaximal activating levels of free Ca++. We measured the effect of AR-L on relations between free Ca++, bound Ca++ and ATPase activity of dog cardiac myofibrils. At pCa 6, 100-300 micrometers AR-L increased myofibrillar ATPase activity maximally by about 30%. The concentration of AR-L giving half-maximal activation of myofibrillar ATPase activity was about 10 micrometers, and is similar to plasma concentrations associated with elevated contractility in intact animals. There was no effect of AR-L on myofibrillar ATPase activity at pCa 5 or 8, and the relation between pCa and percent activation of myofibrillar ATPase activity was shifted to the left by 0.4-0.5 pCa units in the presence of 100 micrometers AR-L. Calcium binding by cardiac myofibrils was increased by AR-L in the presence and absence of MgATP by 0.2-0.3 nmol/mg myofibrillar protein over a broad range of free Ca++ concentrations, a result suggesting that AR-L increases the affinity of myofibrillar troponin C for Ca++. The shift in the pCa giving half maximal and myofibrillar ATPase activity induced by raising the free Mg++ from 1.0 to 10 mm was unaffected by AR-L. These results indicate that the positive actions of AR-L 115BS on cardiac contractility may involve direct activation of myofibrils by virtue of an increased affinity of thin filament receptors for Ca++.

Adenosine Triphosphatases↗
PubMed1982

Calcium antagonists affect calmodulin-dependent contractility of a skinned smooth muscle.

The calcium antagonist prenylamine which had previously been found to inhibit fully the calmodulin myosin light chain kinase systems in concentrations of 200 mumol/l has now been found to inhibit the calmodulin-dependent contraction of skinned smooth muscle (guinea pig taenia coli). The inhibition by prenylamine is itself calcium-dependent. At maximum activation with Ca2+ and calmodulin, little inhibition is observed. Verapamil as well as prenylamine in small concentrations (less than 10 mumol/l) have been found to increase the rate of calcium-induced isometric tension development.

Animals↗
PubMed1981

Vanadate and phosphate ions reduce tension and increase cross-bridge kinetics in chemically skinned heart muscle.

Tension development, immediate stiffness and ATPase of chemically skinned myocardial strips were measured in solutions with varying concentrations of phosphate (Pi) or vanadate (predominantly H2VO4 at pH 7) ion. Vanadate and Pi decreased stiffness in proportion to tension. The results show that, like Pi, vanadate accelerates the turnover rate of cross-bridges, but is effective at about 1/500 the concentration required for the Pi effect. Both Pi and vanadate increased the energy cost of isometric tension maintenance (that is, the ratio of ATPase to tension) and increased the velocity of delayed tension development following quick stretch of the chemically skinned myocardial strips. The results also show that changes in the rate of rise of delayed tension during stretch activation probably reflect changes in the kinetics of the biochemical cycle of the cross-bridges.

Animals↗
PubMed1981

Cyclic-AMP mediated relaxation of chemically skinned fibers of smooth muscle.

Smooth muscle from guinea pig taenia coli was chemically skinned with Triton X-100 and stored in ATP-salt solution containing 50% glycerol at -20 degrees C. Fiber bundles were relaxed at Ca2+-concentrations below 10(-7) M, but contracted at 10(-6) M Ca2+. The isometric tension developed could be partly relaxed by the addition of c-AMP (in the presence of NaF), and it could also be inhibited following preincubation with the catalytic subunit of c-AMP dependent protein kinase. The inhibitory effect was much more pronounced at intermediate Ca2+-concentrations (e.g. 10(-6)) than at concentrations producing a maximum contraction, suggesting that Ca-sensitivity had been lowered. Sodium fluoride which was required to potentiate the c-AMP effects was found to have a slight relaxing effect per se. The c-AMP effect may be mediated through activation of cyclic AMP-dependent kinase, producing, phosphorylation of the myosin light chain kinase which, according to Adelstein et al. (1978), may result in a net dephosphorylation of the myosin light chains and a concomittant inhibition of the contractile response.

Adenosine Triphosphatases↗
PubMed1981

Cyclic AMP inhibits contractility of detergent treated glycerol extracted cardiac muscle.

Glycerinated myocardial fibres treated with a detergent (Lubrol WX) and suspended in ATP salt solution produce half maximum isometric tension at pCa 6.2 (at pH 6.7). After addition of cyclic AMP (1-100 microM), the pCa required for half maximum activation is 5.9. c-AMP in concentrations of 1-100 microM induces a dose dependent inhibition (up to 40% at pCa6), and this effect can be amplified by the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine) 10(-4) M. The effect is similar in presence and absence of sodium fluoride 10 mM. Since in detergent treated skinned fibres the cell membrane and the sarcoplasmic reticulum are extracted and since the Ca2+ ion concentration was kept constant and buffered, we propose that c-AMP does not act via the cell membrane or the sarcoplasmic reticulum, but via phosphorylation of troponin I. The latter is the only component which becomes phosphorylated in skinned fibres during c-AMP induced relaxation, an effect which is also responsible for the inhibition of actomyosin ATPase at constant Ca2+ ion concentration (cf. Ray and England 1976).

Animals↗
PubMed1981

Inorganic phosphate promotes relaxation of chemically skinned smooth muscle of guinea-pig Taenia coli.

In the presence of calmodulin and phosphate and an ATP-regenerating system, Triton-treated "skinned fibers' of the Taenia coli could be made to contract and relax by step changes of Ca++ within about 30 sec. In the absence of phosphate, relaxation was slower, and during this slow relaxation tension was not maintained actively. The passive tension could be abolished by phosphate (3-6 mM). Phosphate had little effect on contractile tension but decreased the speed of contraction.

Animals↗
PubMed1981

Activating effects of AR-L 115 BS on the Ca2+ sensitive force, stiffness and unloaded shortening velocity (Vmax) in isolated contractile structures from mammalian heart muscle.

2-[(2-Methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS), a new positive inotropic substance, is shown to have direct activating effects upon the Ca2+ sensitive force, stiffness and unloaded shortening velocity of membrane-free, detergent-treated myocardial fibres. At pCa 6.2, application of 7--350 mumol/l AR-L 115 BS (concentrations which are also effective in living papillary muscle) led to a 30-50% increase in force and stiffness and even more in Vmax. A possible intracellular action of the drug on the contractile structures directly is discussed in comparison with the known influences of c-AMP dependent phosphorylation of myocardial regulatory proteins.

Animals↗
PubMed1980

Cross bridge slippage in skinned frog muscle fibres.

Mechanically skinned single fibres of the semitendinosus muscles of Rana esculenta were investigated at ca. 4 degrees C. The fibres were activated by a Ca2+ jump technique, which allowed the development of a steady isometric tension within several seconds of entering a calcium rich solution at 4 degrees C. Sequences of length changes of different duration and amplitude were applied to the fibre. It could be demonstrated that the fibre behaved as a Hookean spring in the case of small amplitude length changes (up to 0.5% L0, ramp duration 0.5 ms) and that a sequence of length changes induced reversible changes in fibre state. In contrast, large stretches (greater than 1% L0) induced a muscle "give" if the stretch were not immediately preceded by a release. The data was interpreted on the basis of a strain induced detachment of cross bridges in combination with a rapid reattachment of presumably the same cross bridges in a discharged position. The rates of strain induced detachment and reattachment depended on the stretch amplitude. At amplitudes exceeding 2% L0 the rates were estimated to be at least several thousands per second.

Actomyosin↗
PubMed1980

ATPase activity in rapidly activated skinned muscle fibres.

The ATPase activity of single mechanically skinned fibres from semitendinosus muscle of Rana esculenta was measured. The method was based on the fluorimetrically detected consumption of NADH inside the fibre. NADH breakdown is caused by the reaction of an ATP regenerating system coupled to an NADH oxidising system. The time resolution was about 5 s. The initial rise in ATPase activity was delayed when a fibre was activated by Ca, and ATPase activity reached its plateau at the same time as fibre tension. An activated fibre that was isolated from the incubation solution by immersing it into oil showed a temporary decrease in tension without corresponding decrease in the ATPase activity.

Adenosine Triphosphatases↗
PubMed1980

Effects of trifluoperazine on smooth muscle actomyosin. Short communication.

Trifluoperazine (TFP) inhibits superprecipitation and ATPase activity of smooth muscle actomyosin. This effect appears not to be due to the inhibitory effect of TFP on the Ca++-dependent modulator and the myosin light chain kinase, which are known to be cofactors required for activation of smooth muscle actomyosin.

Actins↗