Transient Rise In Tension Research Articles

Possible Cause of Nonlinear Tension Rise in Activated Muscle Fiber during Stretching.

Tension in contracting muscle fiber under conditions of ramp stretching rapidly increases, but after reaching a critical stretch Pc sharply decreases. To find out the cause of these changes in muscle fiber tension, we stopped stretching before and after reaching Pc and left the fiber stretched for 50 msec. After rapid tension drop, the transient tension rise not accompanied by fiber stiffness increase was observed only in fibers heated to 25°C and stretched to Pc. Under other experimental conditions, this growth was absent. We suppose that stretch of the fiber to Pc induces transition of stereo-specifically attached myosin heads to pre-power stroke state and when the stretching is stopped, they make their step on actin and generate force. When the tension reaches Pc, all stereospecifically attached myosin heads turn out to be non-stereospecifically, or weakly attached to actin, and are unable to make the force-generating step.

The actions of prolonged exposure to cholinergic agonists on isolated bladder strips from the rat.

The present study was done to explore the cholinergic systems operating in the wall of the isolated rat bladder. In a first set of experiments, bladder strips in vitro were subjected to cumulative concentration-response curve (CRC) to non-selective muscarine agonist carbachol or the partially M2>M3 selective agonist arecaidine to establish optimal concentration to be used thereafter. In a second set of experiments, the effects of drugs (solifenacin, isoproterenol, and mirabegron) were tested on urinary bladder contraction induced by the non-selective muscarinergic agonist carbachol. For both agonists, the contractile responses are qualitatively similar: an initial transient rise in tension followed by complex bursts of high-frequency small 'micro'-contractions superposed on a tonic contraction, with immediate transient 'rebound' contraction after the agonist is washed from the preparation. This rebound contraction is greater with carbachol than arecaidine. Components of the responses to cholinergic stimulation, notably the micro-contractions, were found to be differently stimulated and inhibited by the M3>M2 selective antagonist solifenacin and by the β-adrenoceptor agonists isoprenaline and mirabegron. A physiological role for the muscarinic dependent phasic contractions and the micro-anatomical elements that might be involved are not known but may be related to non-voiding activity observed during filling cystometry in conscious animals related to afferent discharge and possibly sensation. Furthermore, suggestions for the potential impact of these findings and design of further studies in relation to bladder physiology, pharmacology, and pathology are discussed.

Toward a Unified Theory of Muscle Contraction. II: Predictions with the Mean-Field Approximation

The contractile behavior of a single half-sarcomere has been calculated from the lattice model with dimeric myosin and extensible filaments, using the model cycle with two working strokes, explicit Pi-release transitions and faster binding for the second head of the dimer. The mean-field approximation is used to generate independent state probabilities for myosin heads, assuming that the positional symmetry of actin filaments in the half-sarcomere is preserved. This model predicts absolute values of the active tension, stiffness and ATPase of fast fibers and their variation with shortening velocity, the phase-2 tension response to a length-release step and the transient tension rise during ramp stretching, in reasonable agreement with experimental data for frog muscle. It accounts for three observations beyond the reach of traditional models: (i) with elastically stiff myosin, a two-stroke model explains the rate of rapid tension recovery as a function of step size, (ii) slow Pi release from A.M.ADP.Pi after the first stroke generates the flat tension response observed after rapid recovery from a small release step, (iii) a discrete lattice model generates undamped oscillations in the isotonic length response to a force step, as observed when the sarcomeres are highly ordered. The discrete lattice also generates length-dependent oscillations in the tension-length curve and the tension response to ramp shortening, which may be smoothed out if lattice symmetry is broken.

Single skeletal muscle fiber behavior after a quick stretch in young and older men: a possible explanation of the relative preservation of eccentric force in old age

The origins of the smaller age-related decrease in eccentric force compared to isometric and concentric conditions in vivo remain unclear. Could this originate from contractile elements of muscle cells? The main intent of the current investigation was to assess the force behavior of muscle cells with aging, during lengthening. Chemically skinned single muscle fibers (n=235) from m. vastus lateralis of six young (mean age 31.6 years) and six older men (mean age 66.1 years) were maximally activated with pCa 4.5 at 15 degrees C. Maximal isometric force and cross-sectional area were measured allowing the calculation of the tension (T (0)). A quick stretch (2 nm per half-sarcomere length) was applied and caused an immediate increase in tension followed by a decrease and a secondary delayed and transient rise in tension (phase 3); finally, the tension recovered a steady state value (phase 4). The tension enhancements during phase 3 (DeltaT (3)) and phase 4 (DeltaT (4)) were evaluated. The myosin heavy-chain isoform composition of each single fiber was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. DeltaT (3) and DeltaT (4) were preserved in older men for both type I and IIa fibers despite a reduction in T (0). Therefore, the age-related preservation of the tension increments after a quick stretch in single muscle fibers could explain in part the smaller decrease in force during eccentric contractions compared to isometric and concentric conditions in vivo with aging usually observed.

Force generation induced by rapid temperature jumps in intact mammalian (rat) skeletal muscle fibres

We examined the tension (force) responses induced by rapid temperature jumps (T-jumps) in electrically stimulated, intact fibre bundles (5–10 fibres, fibre length ∼2 mm) isolated from a foot muscle (flexor hallucis brevis) of the rat; the muscle contains ∼90 % type 2 fast fibres. In steady state experiments, the temperature dependence of the twitch tension was basically similar to that previously described from other fast muscles; the tetanic tension increased 3- to 4-fold in raising the temperature from ∼2 to 35 °C and the relation between the tetanic tension and the reciprocal absolute temperature was sigmoidal with half-maximal tension at 9.5 °C. A rapid T-jump of 3–5 °C was induced during a contraction by applying an infrared laser pulse (λ= 1.32 μ, 0.2 ms) to the 50 μl trough containing the fibre bundle immersed in physiological saline. At ∼10 °C, a T-jump induced a large transient tension rise when applied during the rising phase of a twitch contraction, the amplitude of which decreased when the T-jump was delayed with respect to the stimulus; a T-jump probably perturbs an early step in excitation-contraction coupling. No transient increase was seen when a T-jump was applied during twitch relaxation. When applied during the plateau of a tetanic contraction a T-jump induced a tension rise to a higher steady tension level; the tension rise after a T-jump was 2–3 times faster than the corresponding phase of the initial tension rise in a tetanus. The approach to a new steady tension level after a T-jump was biphasic with a fast (phase 2b, ∼35 s−1 at 10 °C) and a slow component (phase 3, < 10 s−1). The rates of both components increased (Q10∼3) but their amplitudes decreased with increase of the steady temperature. These results from tetanised intact fibres are consistent with the thesis previously proposed from studies on Ca2+-activated skinned fibres, that the elementary force generation step in muscle is enhanced by increased temperature; the findings indicate that an endothermic molecular step underlies muscle force generation.

Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent.

The main aim of this study was to determine the effects of endothelium removal on tension and intracellular Ca(2+) ([Ca(2+)](i)) during hypoxic pulmonary vasoconstriction (HPV) in rat isolated intrapulmonary arteries (IPA). Rat IPA and mesenteric arteries (MA) were mounted on myographs and loaded with the Ca(2+)-sensitive fluorophore fura PE-3. Arteries were precontracted with prostaglandin F(2alpha), and the effects of hypoxia were examined. HPV in isolated IPA consisted of a transient constriction superimposed on a second sustained phase. Only the latter phase was abolished by endothelial denudation. However, removal of the endothelium had no effect on [Ca(2+)](i) at any point during HPV. The endothelin-1 antagonists BQ-123 and BQ-788 did not affect HPV, although constriction induced by 100 nM endothelin-1 was abolished. In MA, hypoxia induced an initial transient rise in tension and [Ca(2+)](i), followed by vasodilatation and a fall in [Ca(2+)](i) to (but not below) prehypoxic levels. These results are consistent with sustained HPV being mediated by an endothelium-derived constrictor factor that is distinct from endothelin-1 and that elicits vasoconstriction via Ca(2+) sensitization.

Force generation induced by rapid temperature jumps in intact mammalian (rat) skeletal muscle fibres.

We examined the tension (force) responses induced by rapid temperature jumps (T-jumps) in electrically stimulated, intact fibre bundles (5-10 fibres, fibre length approximately 2 mm) isolated from a foot muscle (flexor hallucis brevis) of the rat; the muscle contains approximately 90 % type 2 fast fibres. In steady state experiments, the temperature dependence of the twitch tension was basically similar to that previously described from other fast muscles; the tetanic tension increased 3- to 4-fold in raising the temperature from approximately 2 to 35 degrees C and the relation between the tetanic tension and the reciprocal absolute temperature was sigmoidal with half-maximal tension at 9.5 degrees C. A rapid T-jump of 3-5 degrees C was induced during a contraction by applying an infrared laser pulse (lambda = 1.32 micro, 0.2 ms) to the 50 microl trough containing the fibre bundle immersed in physiological saline. At approximately 10 degrees C, a T-jump induced a large transient tension rise when applied during the rising phase of a twitch contraction, the amplitude of which decreased when the T-jump was delayed with respect to the stimulus; a T-jump probably perturbs an early step in excitation-contraction coupling. No transient increase was seen when a T-jump was applied during twitch relaxation. When applied during the plateau of a tetanic contraction a T-jump induced a tension rise to a higher steady tension level; the tension rise after a T-jump was 2-3 times faster than the corresponding phase of the initial tension rise in a tetanus. The approach to a new steady tension level after a T-jump was biphasic with a fast (phase 2b, approximately 35 s-1 at 10 degrees C) and a slow component (phase 3, < 10 s-1). The rates of both components increased (Q10 approximately 3) but their amplitudes decreased with increase of the steady temperature. These results from tetanized intact fibres are consistent with the thesis previously proposed from studies on Ca2+-activated skinned fibres, that the elementary force generation step in muscle is enhanced by increased temperature; the findings indicate that an endothermic molecular step underlies muscle force generation.

Caffeine and carbachol act on common Ca 2+ stores to release Ca 2+ in guinea-pig ileal smooth muscle

To characterize intracellular Ca 2+ stores, the Ca 2+-releasing effects of caffeine, carbachol and inositol 1,4,5-trisphosphate (IP 3) were compared by measuring the drug-induced tension development in β-escin-skinned longitudinal smooth muscle of guinea-pig ileum. Caffeine (20 mM), carbachol (10 or 100 μM) or IP 3 (40 μM), applied after loading Ca 2+ within intracellular stores, produced a transient rise in tension in a Ca 2+-free solution. This change in tension occurred in response to release of Ca 2+ from the stores. The effect of either caffeine or carbachol was markedly reduced or abolished after preceding application of the other drug. IP 3 was without effect when applied subsequently to caffeine. The effects of carbachol and IP 3 were abolished after combined treatment with ryanodine (30 μM) and caffeine (20 mM) which causes functional removal of caffeine-releasable Ca 2+ stores, but not after combined treatment with ryanodine (30 μM) and carbachol (10 μM). The results suggest that caffeine, carbachol and IP 3 all act on common Ca 2+ stores to release Ca 2+.

Contractile Responses to Histamine and GTPγS in β-Escin-Treated Skinned Smooth Muscle of Guinea Pig Ileum

To characterize the calcium (Ca2+)-releasing effects of histamine and GTP gamma S, the drug-induced tension developments were measured in beta-escin-treated skinned longitudinal smooth muscle of guinea pig ileum. Intracellular Ca2+ stores were loaded with Ca2+ by incubating the muscle for 10 min in a Ca(2+)-containing solution. Histamine (10-100 microM), applied after Ca(2+)-loading, produced a transient rise in tension. The effect of histamine was not preserved after treatment with 20 mM caffeine, a Ca(2+)-store releaser. The effect of histamine was potentiated by GTP; inhibited by GDP beta S, an antagonist of GTP for binding to G-proteins; or heparin, an antagonist of inositol 1,4,5-trisphosphate (IP3) for binding to its receptor; and mimicked by IP3. When GTP gamma S (20 microM) was applied and continued to be present for 15 min, a transient rise in tension followed by a small, sustained rise in tension was elicited. The effect of GTP gamma S was completely inhibited by GDP beta S. The initial, transient component of the biphasic GTP gamma S response was abolished or markedly inhibited after treatment with caffeine, heparin or the calcium ionophore A23187. The present results suggest that histamine and GTP gamma S cause a release of Ca2+ from caffeine-sensitive stores which is mediated by IP3 formed through a G-protein-coupled mechanism. The GTP gamma S-induced Ca2+ release is not considered to involve such an IP3-independent process as described in chemically-skinned arterial muscle.

SR Ca loading in cardiac muscle preparations based on rapid-cooling contractures

The influence of rest periods on twitches and rapid-cooling contractures (RCCs) was examined in trabeculae from rabbit, rat, guinea pig, and frog ventricle and rabbit atrium. RCCs were used as a relative index of sarcoplasmic reticulum (SR) Ca content. After increasing rest duration, rabbit and guinea pig ventricles exhibit a decline of both twitch force and RCC force (rest decay). When stimulation is resumed, both twitches and RCCs recover to steady-state levels. The SR (and cells) in these tissues may lose Ca during quiescence and become reloaded with progressive stimulation. Rat ventricle and rabbit atrium exhibited an increase in both twitch and RCC tension as a function of rest duration (rest potentiation). Resumption of stimulation resulted in parallel declines of both twitch and RCC tension approaching steady state. Thus stimulation in rat ventricle and rabbit atrium may lead to a net Ca loss from the SR (and the cell) and quiescence may lead to replenishment of cellular Ca. This major difference in Ca metabolism in mammalian cardiac muscles might be due to a fundamental difference in SR properties or, alternatively, different sarcolemmal transport properties (e.g., action potential configuration, Na-pump). After long rest intervals in rabbit and guinea pig ventricle, RCCs return toward their steady-state value in considerably fewer beats than does twitch tension. This implies that something other than SR refilling is responsible for the slow phase of twitch recovery after rest. In rabbit ventricle increasing frequency or extracellular Ca concentration ([Ca]o) generally increases both twitch and RCC tension. However, decreasing [Ca]o (to 0.2 mM) does not decrease RCCs much despite a dramatic decline in twitch tension (suggesting low twitch tension despite a loaded SR). Rapid rewarming during an RCC usually results in a transient rise in tension (or rewarming "spike"), which is due to a warming-induced increase in myofilament Ca sensitivity. Differences in rewarming spikes among the tissues studied suggest differences in temperature effects on myofilament Ca sensitivity.

Analysis of caffeine action in single trabeculae of the frog heart.

Effects of caffeine on contractile tension and on intracellular action and resting potentials were examined in single frog heart trabeculae suspended in a rapid perfusion chamber. Trabeculae from atria responded more readily than those from ventricles and were therefore studied in greater detail. Both the contracture and twitch responses, the one obtained at high (greater than or equal to 10mM), the other at low (less than or equal to 10mM) caffeine concentrations, consisted of a transient tension rise followed by a maintained phase of lower, but still enhanced, tension. The hypothesis was tested that the transient response is due to the release of calcium from the sarcoplasmic reticulum (s.r.) whereas the maintained tension results from enhanced calcium influx through the cell surface. Support for these ideas was obtained by examining the response to step changes of external calcium and caffeine concentrations, applied in various combinations, simultaneously and in sequence. It also emerged tht the effects on twitch tension of calcium derived from (a) s.r. discharge and (b) influx are additive, to a first approximation. A test procedure for monitoring the s.r. store content was evolved to follow the accumulation of s.r. calcium after a preceding depletion. The results obtained, and others, suggest that the s.r. calcium pump can be operative in atrial heart cells and capable, after store depletion, of reabsorbing up to some 40% of calcium activating a twitch, the remainder being, presumably, extruded from the cells.

ELECTRICAL AND MECHANICAL RESPONSES IN DEEP ABDOMINAL EXTENSOR MUSCLES OF CRAYFISH AND LOBSTER.

Electrical and mechanical studies have been made of the deep abdominal extensor muscles, medial (DEAM) and lateral (DEAL), of crayfish and lobster. The medial muscle responds to direct (intracellular) and indirect stimulation with a transient membrane depolarization which exhibits the properties of a propagated non-decremental action potential but does not overshoot the zero level. The amplitude is about 30 mv in crayfish and 50 mv in lobster. It is followed by a fast all-or-none twitch whose duration at 20 degrees C is 30 to 50 msec. and whose developed tension is 500 gm/cm(2) or about half the tetanic value. Membrane potential is K(+)-dependent and immersion in high K(+) induces a brief transient tension rise as in other twitch-type muscles. The action potential and twitch are normal even if all external Na(+) is replaced with sucrose but vary with external Ca(++), the action potential increasing 8 to 10 mv for a twofold increase in Ca(++). The lateral muscle (DEAL) is much slower and responds to intracellular stimulation only with an electrotonic or a local response. Mechanical responses and relaxation speeds are slow with minimal duration of contraction of 0.5 to 2 seconds. Immersion in high K solutions induces large maintained tensions. Sarcomere length in the fast DEAM is uniform and about 2 micro at rest, but in the DEAL speed is less and sarcomere length is greater averaging about 4.5 micro but with a mixed population of fibers.

Potassium-induced contracture and calcium exchange in the guinea pig's taenia coli.

High potassium (40 mm)-induced tension declined after calcium concentration in the medium (Ca0) was reduced below 1.25 mm, reaching equilibrium level which was dependent on Ca0. High K applied after reduction of Ca0 (0.156–0.94 mm) caused a transient tension rise followed by decline to the same equilibrium level as above. In the presence of 2,4-dinitrophenol (0.3 mm), a transient contraction occurred after high K followed by a decline to a low equilibrium tension which was not dependent on Ca0 (0.156–2.5 mm). Rate constants of Ca45 outflow were not markedly affected by high K. Ca45 uptake and exchangeable fraction of cellular Ca increased with high K. Results suggest the release of Ca during K contracture.