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PubMed2005

Effects of ouabain on contractions induced by manganese ions in C2+a-free, isotonic solutions with varying concentrations of K+ in guinea-pig taenia coli.

The action of ouabain, a cell membrane Na+, K+-ATPase blocker, on contractions induced by manganese ions (Mn2+) in Ca2+-free, isotonic solutions with varying concentrations of K+ in the external medium were investigated in order to evaluate the underlying role of external Na+ in Mn2+-induced contractions in isolated taenia coli of the guinea-pig. Mn2+ at 5 mM induced greater contractions as external isotonic K+ concentrations progressively increased from 10 to 100 mM. Ouabain (2 x 10(-4) M) completely inhibited tension development stimulated by 5 mM Mn2+ in isotonic, 30 mM K+ (96 mM Na+) medium. Whereas, the tension inhibitory effects of ouabain became progressively weaker as isotonic, external K+ concentrations increased to 60 mM, which successively decreased external Na+ concentrations. Eventually, ouabain failed to affect contractions stimulated by Mn2+ in isotonic, 126 mM K+, Na+-deficient medium. Ouabain caused progressively greater increase in cellular Na+ concentrations as the Na+ concentrations increased in the isotonic, K+ medium. While, pyruvate, which penetrates cell independently of external Na+, reversed the inhibition of tension by ouabain in isotonic, 30 mM K+, Na+-sufficient (96 mM) medium containing 5 mM Mn2+. These results suggested that Mn2+ induced the contraction, which was maintained by glucose transport depending on external Na+, in the case of Na+-sufficient medium in K+-depolarized taenia coli. However, it induced the contraction independent of external Na+, in the case of Na+-deficient, K+ medium. Ouabain might exhibit greater inhibition of the contraction induced by Mn2+ as the decrease in the Na+ gradient across the cell membranes continues.

Animals↗
PubMed1998

Bladder motility and efferent nerve activity during isotonic and isovolumic recording in the cat.

1. Bladder motility and pelvic nerve efferent activity were recorded in anaesthetized cats under isotonic or isovolumic conditions. In isotonic conditions the bladder was connected to a reservoir and fluid entering or leaving the bladder was monitored for 8 min using different heads of pressure (isotonic recording). Under isovolumic conditions fixed volumes were injected into the bladder and pressure changes recorded (micturition contractions). 2. In isotonic conditions, at low pressures the bladder filled to a roughly constant level, and then developed small amplitude oscillatory contractions. At higher pressures, after the initial filling, the bladder contracted, expelling part of its volume. Depending on the pressure this contraction was either sustained or led to a gradual expansion of the bladder. In both cases transient periods of expansion were superimposed. In contrast after an initial slow build up, the efferent nerve activity increased reaching a sustained level of activity during which transient decreases in rate were seen. 3. The firing frequency of the efferent nerve activity during the sustained phase increased as the intravesical pressure was raised until a plateau was reached at high pressures. The plateau pressure (Pplateau) in a bladder was positively correlated with the peak pressure reached by the bladder during micturition contractions under isovolumic conditions, suggesting that micturition contractions were produced by the maximum output of the reflex pathway. 4. Section of the hypogastric nerves had relatively little effect, but additional section of the pelvic nerves abolished the contractile phase of the bladder response to filling, and resulted in continuous filling of the bladder. 5. The transient bladder expansions (duration, 3-33 s) seen when the innervation was intact were closely related to the transient decreases in efferent nerve activity, suggesting involvement of a central inhibitory mechanism. The threshold pressure for triggering transient expansions was similar to the pressure shown to activate myelinated afferent fibres. 6. Under isovolumic conditions the frequency of micturition contractions increased with increasing vesical volume, and the relaxed interval between contractions shortened. This response could also be evoked by stimulation of the central cut end of the pelvic nerves, suggesting that the central inhibitory mechanism could also be active during isovolumic conditions.

Animals↗
PubMed1981

The calcium antagonistic effects of cyproheptadine on contraction, membrane electrical events and calcium influx in the guinea-pig taenia coli.

1 The ability of cyproheptadine (Cph) to inhibit membrane translocation of calcium in smooth muscle was investigated by studying the drug's action on contraction, electrical activity and calcium influx in the guinea-pig taenia coli.2 Cph >/= 10(-6)M reduced the amplitude of normal spontaneous contractions and concurrently decreased the number of action potentials occurring with each slow-wave of depolarization (sucrose-gap recordings). These inhibitory effects of Cph were antagonized by increasing the medium [Ca] three fold to 7.68 mM.3 Intracellular recordings showed that Cph >/= 2 x 10(-6)M decreased the amplitude and extended the duration of the action potential. These effects were only partially reversible in normal medium whereas large overshooting action potentials were again seen in 7.68 mM Ca medium.4 High frequency mechanical activity was produced by inclusion of veratridine 5 x 10(-6)M in the perfusate. Low concentrations of Cph (>/= 10(-7)M) reduced the amplitude of such contractions at a faster rate than they did normal spontaneous contractions.5 At concentrations between 10(-7) and 10(-6)M, Cph fully reduced the tonic component of contractions elicited in 112 mM isotonic KCl whilst having little or no effect on either (i) the initial phasic KCl contraction or (ii) the ;repolarization contracture' normally produced on wash-out of the KCl or (iii) the spontaneous contractions before and after KCl treatment. In contrast, at Cph 2 x 10(-6)M, the repolarization contracture, as well as the isotonic KCl contraction, was totally blocked whereas spontaneous contractions were still unaffected. Progressively higher Cph concentrations inhibited all components of this contractile cycle.6 Dose-response curves for the rate of drug-induced relaxation of tonic contractures produced in hypertonic 42.7 mM high-potassium medium, showed the calcium antagonistic potency of Cph to be intermediate between that of chlorpromazine and D600. The minimum Cph concentration for effect lay between 1 and 5 x 10(-7)M, and the effects of Cph 2 x 10(-6)M (approximately the ID(50)) were totally antagonized by 12.8 mM Ca.7 By means of a lanthanum wash procedure, Cph >/= 2 x 10(-6)M was found to decrease the (45)Ca uptake occurring into strips of taenia coli in normal medium, although the maximum effect (at Cph 10(-5)M) amounted to only 25% inhibition of the uptake occurring into control strips (also found with D600). The increased uptake occurring in hypertonic 44.7 mM high-potassium medium was inhibited in a dose-dependent manner by Cph 1 x 10(-7)M.8 The results are consistent with an action of Cph in reducing the flow of Ca(2+) through voltage-dependent Ca channels in the smooth muscle cell membrane. It is suggested that the interaction of Cph molecules with such sites is dependent upon membrane potential as well as drug concentration.

Animals↗
PubMed1989

Oxidation/reduction state of cytochrome oxidase during repetitive contractions.

There is disagreement regarding whether inadequate O2 determines maximal O2 uptake (VO2max) and lactic acid output (L) during muscular activity. Direct assessment of mitochondrial cytochrome oxidase (cytochrome a-a3) oxidation/reduction (O/R) state should provide an unequivocal answer for this issue. A new near-infrared spectrophotometric method was used to measure the O/R state of cytochrome a-a3 of dog gastrocnemius-plantaris muscle in situ during repetitive isotonic twitch and tetanic contractions. Three contraction frequencies were used for each contraction type in alternating sequence to provide a wide range of VO2 up to VO2max. VO2 and L were measured after 3 and 9 min of a 10-min contraction period, and 15 min were allowed for recovery between contraction periods. VO2 increased with contraction frequency. L was variably increased with contraction frequency at 3 min and uptake usually occurred at 9 min, except at the highest tetanic frequency. The O/R span of cytochrome a-a3 was determined by respiring the animals with 100% N2 to determine the most reduced state. This was followed by respiration with 100% O2, which gave the most oxidized state transiently during recovery. Within this span in muscles at rest, cytochrome a-a3 was 50-80% oxidized. During contractions of both types at all frequencies, cytochrome a-a3 always became more oxidized by an additional 10-20%. These findings should put to rest any arguments that inadequate O2 is a determinant of VO2max or L under the conditions of these experiments: repetitive contractions with free flow in self-perfused muscles and normoxia.

Animals↗
PubMed1981

The initiation of phasic and tonic contraction by potassium and the effect of calcium, multivalent cations and Ca-antagonist on potassium contracture in guinea-pig vas deferens.

The role of Ca in phasic and tonic contractions of high-K-induced contractures of guinea-pig vas deferens was studied. It was shown that phasic contraction was initiated by a burst of action potentials, and tonic contraction by sustained depolarization. Phasic contraction seemed to be related to the rate and degree of depolarization, whereas tonic contraction seemed to be related only to the degree of depolarization. Tonic contraction was more sensitive to a reduction of extracellular Ca, though both types of contraction were abolished by Ca removal. The tonic contraction observed with isotonic recording was more sensitive to extracellular Ca than that observed with isometric recording. Maximum contractions were achieved with lower Ca than that in isometric measurement. Verapamil blocked tonic contraction at a low concentration, and both contractions at a high concentration. Mn or La blocked the phasic and tonic contractions first. After prolonged exposure to either ion, however, tonic contraction could be induced. The results suggest that both phasic and tonic contractions were induced by Ca-influx through the cell membrane, and that tonic contraction was maintained by a constantly elevated intracellular Ca concentration which is the consequence of an altered equilibration of Ca influx and Ca extrusion through the cell membrane.

Action Potentials↗
PubMed1980

Modulation of jejunal flow by solutions of varying osmolality and acidity in the intact canine jejunum.

Because gastric emptying is modulated by the osmolality or hydrogen ion concentration of intraduodenal solutions, we hypothesized that similar mechanisms exist to regulate flow within the small intestine and that the altered flow is associated with changes in intestinal motility. Sodium chloride solutions with higher and lower osmolality than plasma and both isotonic and hypotonic hydrochloric acid solutions flowed more slowly into segments of jejunum in conscious dogs than isotonic neutral salt solutions. The altered flow was associated with increased frequency of spike bursts in the segment with the salt solutions of varied osmolality, but with only increased force of contractions with both isotonic and hypotonic acid solutions. Some evidence exists to suggest that the changes in motility are mediated by a neural mechanism. If similar mechanisms exist in the duodenum, they may play a role in the regulation of gastric emptying.

Action Potentials↗
PubMed2001

A comparison of effects measured with isotonic and isometric recording: II. Concentration-effect curves for physiological antagonists.

If one drug, B, antagonizes another, A, by producing the opposite physiological effect, the antagonist concentration-effect curves should be affected by the recording system, which limits the range of agonist responses. With pieces of isolated guinea-pig ileum taken from adjacent parts of the same animal, one recorded isotonically, the other isometrically with the same load, the isotonic IC(50) values for (-)isoprenaline opposing carbachol or histamine were lower than the isometric values (P<0.01) but there was a significant correlation between them (P<0.01): the isotonic curves were steeper (P<0.01) and there were wider shifts in IC(50) before increasing the agonist reduced the maximum relaxation. In similar experiments with pieces of rat uterus in oestrus from the same animal, the concentration-effect curves for carbachol opposed by increasing concentrations of (-)isoprenaline or (-)adrenaline had slightly lower EC(50) values with isometric recording but there was a significant correlation (P<0.01) with isotonic values. The antagonist effect (ratio of the EC(50) relative to that for the control) was higher with isotonic recording (P<0.01 for (-)isoprenaline, P<0.025 for (-)adrenaline) and all (27) curves were steeper than the corresponding isometric curve (P<0.001). The influence of the method of recording on the results is expected from the narrower operational window and smaller upper limit to relaxation with isotonic recording. A way of obtaining measurements of IC(50) against a standard agonist effect is suggested in an Appendix.

Animals↗
PubMed1994

Regulation of isotonic shortening velocity by second messengers in tracheal smooth muscle.

Evidence suggests that the mechanical behavior of smooth muscle tissues is regulated by Ca(2+)-dependent changes in the phosphorylation of the 20,000-Da light chain of myosin (MLC). However, alternative mechanisms activated by specific kinases may be involved in regulating the shortening velocity in some smooth muscle tissues. To determine how the activation of protein kinases A or C affects the regulation of the shortening velocity in canine tracheal smooth muscle, we evaluated the effects of forskolin (10(-5) M) and phorbol 12,13-dibutyrate (PDBu, 3 x 10(-6) M) on active stress, intracellular Ca2+ ([Ca2+]i), MLC phosphorylation, and isotonic shortening velocity during contractions elicited by 60 mM KCl. Forskolin depressed and PDBu increased active stress, [Ca2+]i, MLC phosphorylation, and shortening velocity; thus the effects of these agents on the shortening velocity may result from changes in Ca(2+)-dependent MLC phosphorylation. In contrast, the decline in velocity that occurred with time during tonic contractions elicited by K+ depolarization was not associated with significant changes in MLC phosphorylation; thus the time-dependent changes in shortening velocity may be regulated by a mechanism other than MLC phosphorylation.

Animals↗
PubMed1988

Changes in left ventricular wall stress during isometric and isotonic exercise in healthy men.

Changes in left ventricular (LV) meridional and circumferential end-systolic wall stress during isometric and isotonic exercises were determined noninvasively in 12 healthy subjects using echocardiography and cuff blood pressure measurements. Isometric exercise was performed at 20 and 40% of maximal voluntary contraction using a handgrip dynamometer, and isotonic exercise was done on a cycle ergometer at 150 kpm/min increments every 3 minutes to a maximum of 600 kpm/min. Although the increase in systolic blood pressure was similar in both forms of exercise, LV systolic stress in the circumferential and meridional planes increased markedly during isometric exercise but decreased slightly during higher intensity isotonic exercise. Isometric exercise also produced a significant decrease in fractional shortening, whereas isotonic exercise significantly increased fractional shortening. Wall stress and fractional shortening were linearly and inversely related, but isometric and isotonic exercise produced divergent and significantly different linear regressions. In normal subjects isometric exercise produces a significant increase in LV afterload that leads to a decrease in LV global function. In contrast, isotonic exercise causes an increase in LV global function, most likely from an unchanged or slight decrease in afterload associated with increased LV contractility from greater catecholamine release.

Adult↗
PubMed2003

Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.

Adolescent↗
PubMed1996

Evidence for mediation by endothelium-derived hyperpolarizing factor of relaxation to bradykinin in the bovine isolated coronary artery independently of voltage-operated Ca2+ channels.

1. The role of endothelium-derived hyperpolarizing factor and voltage-operated Ca2+ channels in mediating endothelium-dependent, NG-nitro-L-arginine (L-NOARG; 100 microM) -resistant relaxations to bradykinin (BK), was examined in isolated rings of endothelium-intact bovine left anterior descending coronary artery. 2. Rings of artery were contracted isometrically to approximately 40% or their respective maximum contraction to 125 mM KCl Krebs solution (KPSSmax) with the thromboxane A2-mimetic, U46619. Relaxations to BK and the endothelium-independent NO donor, S-nitroso-N-acetylpenicillamine (SNAP), were normalized as percentages of reversal of the initial contraction to U46619. All experiments were carried out in the presence of indomethacin (3 microM). 3. BK caused concentration-dependent relaxations [sensitivity (pEC50) 9.88 +/- 0.05; maximum relaxation (Rmax), 103.3 +/- 0.5%] in U46619-contracted rings of bovine coronary artery. L-NOARG (100 microM) caused a significant (P < 0.01) 3 fold reduction in the sensitivity to BK (pEC50, 9.27 +/- 0.11) without affecting the Rmax (101.8 +/- 2.3%). A similar, significant 3 fold reduction in sensitivity to BK with no change in Rmax was observed after treatment with oxyhaemoglobin (20 microM; pEC50, 9.18 +/- 0.13, P < 0.001) or a combination of oxyhaemoglobin (20 microM) and L-NOARG (100 microM; pEC50, 9.08 +/- 0.10, P < 0.001). Oxyhaemoglobin (20 microM) either alone or in combination with L-NOARG (100 microM) caused an approximate 600 fold decrease in the sensitivity to SNAP. 4. The L-type voltage-operated Ca2+ channel inhibitor, nifedipine (0.3 microM-3 microM), reduced the maximum contraction (Fmax) to isotonic 68 mM KCl Krebs solution (103.5 +/- 2.0% KPSSmax) by 85-90% (P < 0.001); yet, the highest concentration of nifedipine (3 microM) caused only a small but significant reduction in both the sensitivity and Fmax to U46619. By contrast, nifedipine (3 microM) had no effect on the relaxation response to BK. Furthermore, a combination of nifedipine (3 microM) and L-NOARG (100 microM) had no further inhibitory effects on relaxations to BK (pEC50, 8.79 +/- 0.10; Rmax, 101.7 +/- 2.4%) than did L-NOARG (100 microM) alone (pEC50, 9.05 +/- 0.12; Rmax, 99.62 +/- 1.19). Also, nifedipine (0.3 microM and 3 microM) had no effect on the maximum relaxation to the K+ channel opener, levcromakalim (0.3 microM). 5. In the presence of nifedipine (0.3 microM to control contractions induced by high KCl) and isotonic 68 mM KCl Krebs solution (to inhibit K+ channel activity), relaxations to BK (pEC50, 9.42 +/- 0.10; Rmax, 93.9 +/- 1.8%) were similar to those observed in normal Krebs solution (pEC50, 9.58 +/- 0.09; Rmax, 98.4 +/- 0.8%). However, in the presence of 68 mM KCl Krebs solution the inhibitory effect of L-NOARG (100 microM) on relaxations to BK (pEC50, 8.53 +/- 0.20; Rmax, 31.0 +/- 11.3%) was markedly greater than that in normal KCl Krebs solution (pEC50, 9.12 +/- 0.08; Rmax, 91.5 +/- 2.0%). Similar treatment with 68 mM KCl Krebs had no effect on relaxations to the NO donor, SNAP, yet abolished the response to the K+ channel opener, levcromakalim (0.3 microM). 6. In summary, this study has shown that (1) NO synthesis in response to BK in bovine coronary artery endothelial cells in situ is likely to be abolished by L-NOARG, (2) NO-independent relaxations to BK are markedly attenuated by 68 mM KCl-containing Krebs, which, in the absence of L-NOARG, had no effect, (3) nifedipine blocked contractions to a maximum-depolarizing stimulus (KCl) yet had no effect on NO-independent relaxations to BK, and (4) maximum relaxations to levcromakalim were abolished by 68 mM KCl Krebs but were not affected by nifedipine. Therefore, we hypothesize that if smooth muscle hyperpolarization is involved in non-NO-, endothelium-dependent relaxation in bovine coronary arteries contracted with U46619, then it can accomplish this via a mechanism which does not i

Animals↗
PubMed1994

Power output of scallop adductor muscle during contractions replicating the in vivo mechanical cycle.

Because measurements on isolated skeletal muscles are often made with limited knowledge of in vivo kinematics, predictions of mechanical performance during natural movements are subject to considerable uncertainties. We used information on the in vivo length cycle and phase of activation of the scallop adductor during swimming at 10 degrees C to design an in vitro contractile regime that replicated the natural cycle. Replicating the in vivo length cycle and stimulation regime resulted in power output during cyclic contractions that matched in vivo performance both qualitatively and quantitatively. When sinusoidal length changes were used instead of the natural length trajectory, the adductor muscle produced a similar average power output (approximately 30 W kg-1 at 1.9 Hz), but the distribution of power throughout the cycles was quite different. We examined the instantaneous force-velocity properties during cyclic contractions and found that the muscle operated on or near its isotonic force-velocity curve for only 30-40% of the time required for shortening. During sinusoidal length cycles, the force-velocity trajectory was quite different. We conclude that during cyclic contractions the isotonic force-velocity curve of skeletal muscle sets an approximate boundary to the force-velocity trajectory, but the shape of this trajectory, and thus the distribution of power output, depends on the pattern of length change.

Animals↗
PubMedDate not supplied

Effects of AR-L 115 on contraction and relaxation of isolated mammalian cardiac muscle.

We studied the mode of action of a new cardiotonic agent (AR-L115) contractile performance of isolated cardiac muscle. We analyzed its effects on the contraction and relaxation of partially skinned, single cardiac cells of rat ventricle, and of intact papillary muscles of the right ventricle of the cat. AR-L115 (30-100 micrograms/ml) reversibly increased the frequency, but not the amplitude, of spontaneous isotonic and isometric contractions of the single cells with functioning sarcoplasmic reticulum (SR), thereby resembling the action of caffeine. It did not affect contractions of mechanically skinned and detergent-pretreated cells without functioning SR, which were activated through iontophoretic calcium pulses. In papillary muscles, AR-L115 (1-40 micrograms/ml) significantly increased directly measured maximum unloaded velocity of shortening at zero load, peak velocity of isotonic shortening and lengthening, peak total isometric tension development, and peak rate of tension development, indicating augmented contractility. These effects were less pronounced than those of increasing the calcium concentration in the bathing solution from 2.5 to 7.5 mM. After beta-adrenergic blockade (propranolol or toliprolol 10(-5) M), the maximal effects of AR-L115 were markedly diminished. Load dependence of isotonic relaxation and the time of half-isometric relaxation were not affected by the drug. Accordingly, AR-L115 is a mild positive inotropic agent, which mainly increases contractility during the contraction phase without markedly affecting load dependence of relaxation. These effects are probably mediated both through a catecholaminelike action on beta-receptors and through a separate caffeinelike action on the calcium-sequestering membrane systems. In contrast to digitalis glycosides, AR-L115 does not exhibit tachyphylaxis in chronically AR-L115-loaded animals.

Adrenergic beta-Antagonists↗
PubMed1984

Short-term memory in the in situ canine myocardium.

We studied the effect of intracycle (short-term) mechanical history on canine myocardial performance. Intracycle muscle force and/or length history was varied, and the resultant changes in end-systolic force-length relationship were analyzed. Antecedent isotonic shortening impaired, whereas isometric force development enhanced end-systolic myocardial performance. A history of shortening concurrent with force development produced an intermediate effect. We conclude that decreasing force or length impairs whereas increasing length or force enhances performance in the same cycle. Different combinations of antecedent force and length changes affect end-systolic performance by algebraic summation (superposition) of their disparate effects. Time measurements established that 1) total systolic time varied little with altered history, 2) isotonic shortening took longer than isometric contraction in reaching a point P in the force-length plane, and 3) less time was therefore available for contraction after P with antecedent isotonic shortening than with antecedent isometric force development. This history-dependent time differential accounts for the corresponding differential in performance.

Animals↗
PubMed1998

Shortening versus isometric contractions in isolated human failing and non-failing left ventricular myocardium: dependency of external work and force on muscle length, heart rate and inotropic stimulation.

BACKGROUND: For reasons of simplicity, studies on isolated human myocardium have been conducted using exclusively isometric contractions, although positive inotropic interventions may differently influence force development, extent of shortening and myocardial work performance. We investigated human left ventricular failing and non-failing preparations comparing isometric versus isotonic, i.e., shortening contractions. RESULTS: (1) When muscle length is increased from 90% to 100% lMAX, peak developed force increases by 36% and 43% (p < 0.05) in non-failing and failing human left ventricular myocardium, respectively. Maximum performed work increases similarly in non-failing but decreases in failing myocardium. It can be shown that this discrepancy is due to significantly higher resting tension and does not present an insufficient intrinsic shortening capacity in failing myocardium. (2) When stimulation rate is increased from 0.5 to 2.0 Hz, isometric force increases significantly by 59% in non-failing and decreases by 27% in failing myocardium, whereas maximum performed work increases by 98% and decreases by 46%, respectively. (3) Pharmacological positive inotropic interventions by 7.2 mM calcium (n = 9), 3 x 10(-8) M isoproterenol (n = 7), 3 x 10(-8) M ouabain (n = 5), and 10(-5) M EMD 57033 (n = 3) equally increased force development and extent of shortening: When the fractional effect on shortening (y) was correlated to the fractional effect on force (x), the following linear regression equation was obtained: y = 0.91x + 0.26 (r = 0.86; p < 0.001). CONCLUSIONS: The data presented are of clinical and pharmacological importance: (1) The Frank-Starling mechanism is demonstrated to be existent in the failing human myocardium regarding both isometric force developed and maximum work performed. (2) Both force-frequency relations and--to a greater extent--work-frequency relations are reversed in failing human myocardium. (3) Independent of the pharmacological mode of action, positive inotropic compounds increase developed isometric force to the same extent as isotonic shortening and therefore potentiate maximum performed work.

Adolescent↗
PubMed1975

Electrical and mechanical properties of longitudinal and circular muscles of the guinea-pig ileum.

The membrane potential of the electrically quiescent circular muscle fibre is higher than that of the spontaneously active longitudinal muscle fibre. The length constant of circular muscle fibres is longer than that of the longitudinal muscle. The electrical activity of the longitudinal muscle membrane is enhanced by caffeine and PGE1 is suppressed for the circular muscle. Isotonic K Krebssolution generates a large tonic response of the contracture of longitudinal muscle tissue, but in circular muscle it is small. Following an inward current pulse, a large rebound contraction of the circular muscle was generated during K-INDUCED CONTRACTURE BUT IT WAS SMALL IN THE LONGITUDINAL MUSCLE TISSUE. Caffeine suppressed the K-induced contracture of both tissues but enhanced the rebound contraction of the circular muscel. Verapamil and lanthanum suppressed the mechanical responses of both muscle tissues but rebound contraction evoked in isotonic K Krebs solution was of longer duration in circular muscle tissue than in longitudinal muscle tissues. It is postulated that both muscle tissues possess different electrical and mechanical properties, and that these differences are not caused by nervous activity.

Animals↗
PubMed1995

X-ray evidence that in contracting live frog muscles there exist two distinct populations of myosin heads.

Using synchrotron radiation and whole muscles, 2 ms time-resolved x-ray diffraction patterns were recorded at 8 degrees C. The results show that in both isotonic and isometric contractions, as well as in length changes imposed at maximum tension [Po], the meridional third myosin layer line consists of two distinct reflections with different intensities and spacings that measure approximately 14,623 and 14,412 nm at Po. Although the intensity behavior of the two reflections is strikingly different during quick releases, it is very similar during stretches. Study of the time courses indicates that myosin heads diffracting at Po with the approximately 14.623 nm periodicity are actively involved in tension production. Those diffracting at Po with the periodicity of approximately 14.412 nm appear not be associated with tension production during isometric contraction and releases, but the results suggest that they are recruited during stretches and here contribute to tension production. Our most important conclusion is that under all conditions of contraction we have investigated there exist two populations of myosin heads, each with a well defined axial disposition and configuration.

Animals↗
PubMed1975

Structural changes in myosin during contraction and the state of ATP in the intact frog muscle.

The reactivity of myosin to [14C]-labeled N-ethylmaleimide ([14C]NEM) or to tritium was determined in functionally different frog muscles. The incorporation of [14C]NEM into myosin decreased during isotonic or isometric contractions, as compared to resting muscle. The cysteine residues which were protected during contraction were not involved in the ATPase activity or the actin-binding ability of myosin. Peptide mapping revealed that several residues were protected simultaneously. The incorporation of tritium into the peptide N-H groups of myosin was also decreased during muscle activity. These data support the idea that activation and subsequent contraction of muscle are correlated with structural changes in the myosin molecule. The reactivity of myosin to [14C]NEM was increased when the muscle was stretched to 140% rest length and treated with iodoacetate to deplete ATP. Based on in vitro experiments and on literature data, it is suggested that in the resting muscle myosin contains bound MgATP which decreases the rate of incorporation of [14C]NEM into myosin and that upon the irreversible loss of ATP the rate increases. 31P nuclear magnetic resonance signals from a number of phosphates were detected in the intact frog muscle. The data indicated that the minimum concentration of ATP in the muscle is 3 mM, a value which agrees with that of chemical determination. The characteristic chemical shifts, coupling constants, and line widths of ATP in the muscle were considerably altered from that of either free ATP in aqueous solutions or ATP in perchloric acid extracts of muscle.

Actins↗