Changes In Contractile Activity Research Articles

Increased cyclic AMP content accelerates protein synthesis in rat heart.

Elevation of cyclic AMP (cAMP) content in perfused rat hearts by exposure to glucagon, forskolin, and 1-methyl-3-isobutylxanthine (IBMX) increased rates of protein synthesis during the second hour of perfusion with buffer that contained glucose in the absence of added insulin. When tetrodotoxin was added to arrest contractile activity, glucagon, forskolin, and IBMX still elevated cAMP content and rates of protein synthesis. Perfusion of beating rat hearts at elevated aortic pressure (120 mm Hg vs. 60 mm Hg) also accelerated rates of protein synthesis and raised cAMP content and cAMP-dependent protein kinase activity during the second hour of perfusion. Insulin accelerated rates of protein synthesis in beating hearts during the first and second hour of perfusion but did not increase cAMP content. Elevation of aortic pressure in insulin-treated hearts raised cAMP content but had no further effect on rates of protein synthesis. Perfusion of arrested hearts for as little as 2 minutes at 120 mm Hg resulted in a rapid and sustained increase in cAMP content, cAMP-dependent protein kinase activity, and rate of protein synthesis after 60-120 minutes of additional perfusion at 60 mm Hg. Exposure of arrested hearts to 0.2 mM methacholine, a muscarinic-cholinergic agonist, for 5 minutes before elevation of perfusion pressure blocked the pressure-induced increases in cAMP content, cAMP-dependent protein kinase activity, and rates of protein synthesis. When hearts were removed from pertussis toxin-treated animals, methacholine did not block the effects of forskolin on these same three parameters. These studies indicated that elevation of tissue cAMP by hormone binding, direct activation of adenylate cyclase, or inhibition of phosphodiesterase resulted in acceleration of protein synthesis. Furthermore, the effects of increased aortic pressure to accelerate synthesis appeared to involve a cAMP-dependent mechanism that was independent of changes in contractile activity but could be blocked with a muscarinic-cholinergic agonist. Acceleration of protein synthesis by insulin was not associated with an elevation of cAMP.

Effects of inhibition of mitochondrial protein synthesis in skeletal muscle.

To evaluate the participation of proteins derived from mitochondrial genes in the adaptive response of skeletal muscle to increased contractile activity, we administered chloramphenicol (CAP; 200-1,000 mg.kg-1.day-1), an inhibitor of translation from mitochondrial ribosomes, to adult rabbits undergoing electrical stimulation of the tibialis anterior muscle of one hind limb. In unmedicated animals, 10 days of electrical stimulation increased maximum velocity (Vmax) of cytochrome oxidase and citrate synthase by 214 +/- 17 and 201 +/- 16% (P less than 0.01). In a dose-dependent manner, CAP abolished activity-induced increases in cytochrome oxidase Vmax, suggesting that augmented mitochondrial protein synthesis is necessary for the adaptive response of enzymes that require protein subunits encoded by mitochondrial genes. However, CAP failed to inhibit activity-induced changes in Vmax of enzymes derived exclusively from nuclear genes (citrate synthase and aldolase). CAP also failed to inhibit activity-induced increases in mRNA transcribed from the nuclear genes encoding beta-F1 ATPase or myoglobin, or from the mitochondrial genes encoding 12S rRNA, 16S rRNA, or cytochrome b. These latter findings suggest that mitochondrial translation products do not participate in pretranslational regulation of these nuclear or mitochondrial genes in response to changes in contractile activity of skeletal muscle.

Seasonal changes in contractile activity of a toxic substance from the pedicellaria of the sea urchin Toxopneustes pileolus

The seasonal change in the activity of an extract from the pedicellariae of the sea urchin Toxopneustes pileolus was investigated in terms of contraction of the longitudinal muscle of the isolated guinea-pig ileum. The protein level of the crude extract from the pedicellariae was high in May, June and July, but was not parallel to the activity of the extract which was low in summer (0.03 × 10 3−0.33 × 10 3) and became higher in autumn and winter (0.51 × 10 3 − 1.1 × 10 3). The changes in protein level and the specific activity of the extract were also not closely correlated to the reproductive season of the sea urchins. The specific activity of Peak II fraction purified from the extract was high in spring (May), lowest in summer and elevated again in autumn and winter.

6] Myosin light chain phosphorylation in smooth muscle and nonmuscle cells as a probe of calmodulin function

The function of Ca2+-calmodulin-dependent phosphorylation of phosphorylatable myosin light chain (P-light chain) is currently an area of immense interest and research. In the smooth muscle, P-light chain phosphorylation is a requisite for the interaction of myosin with actin. One major problem in working with intact smooth muscle or nonmuscle cells has been the lack of a sensitive technique for quantitating the extent of P-light chain phosphorylation in preparations that are routinely used in physiological and pharmacological investigations. This chapter discusses methodology for quantitating P-light chain phosphorylation during changes in isometric tension development of the bovine tracheal smooth muscle. The applicability of the methodology for quantitating P-light chain phosphorylation in various types of vascular smooth muscles, cardiac muscle, and skeletal muscles has also been determined in the chapter. This methodology should also be adaptable to other tissues or nonmuscle cells, such as platelets and macrophages, where myosin P-light chain phosphorylation may be involved in the regulation of motile processes. The combined use of pyrophosphate gel electrophoresis, isoelectric focusing, and ammoniacal-silver staining offers a relatively rapid, accurate, and sensitive technique for quantitating the extent of P-light chain phosphorylation during changes in contractile activity in the smooth muscle.

Postprandial changes in contractile activity and bile concentration in gallbladder of the dog.

ARTICLESPostprandial changes in contractile activity and bile concentration in gallbladder of the dogI. Takahashi, M. Nakaya, T. Suzuki, and Z. ItohI. Takahashi, M. Nakaya, T. Suzuki, and Z. ItohPublished Online:01 Nov 1982https://doi.org/10.1152/ajpgi.1982.243.5.G365MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Video Abstract More from this issue > Volume 243Issue 5November 1982Pages G365-G371 Copyright & PermissionsCopyright © 1982 the American Physiological Societyhttps://doi.org/10.1152/ajpgi.1982.243.5.G365PubMed7137353History Published online 1 November 1982 Published in print 1 November 1982 Metrics

Beta-blockade and ischaemic injury: effects of partial agonist activity.

In this study we have attempted: firstly to assess the extent to which the presence of partial agonist activity in a beta-blocking compound and/or sympathetic drive, influence ischaemic injury, and secondly to determine if any of the observed differences are due to changes in contractile activity. In the isolated, globally ischaemic (low flow) rat heart, oxprenolol (which possesses partial agonist activity) did not reduce creatine kinase leakage to the same extent as propranolol (no partial agonist activity) regardless of the background level of catecholamine drive. However, increasing background catecholamine drive increased the relative protection against enzyme leakage, of both beta-blockers. Under conditions of zero contractile activity (high K+ - medium) neither beta-blocker reduced enzyme leakage. Thus at equi-blocking doses oxprenolol and propranolol reduce enzyme leakage to different extents and the lesser protection afforded by oxprenolol is likely to be attributed to the presence of partial agonist activity. In addition, the reduction in enzyme leakage caused by both these compounds is due to reductions in contractile activity.

Analysis of mechanisms of the positive inotropic action of a protein antigen (egg albumin) and histamine on the myocardium of sensitized guinea pigs

Changes in contractile activity of the myocardium during the local anaphlactic reaction and the action of histamine were investigated in preparations of the left auricle of guinea pigs sensitized beforehand with egg albumin. Histamine (1\10−5 g/ml) and egg albumin (2\10−5 g/ml) caused little change in the first (after 3 min of rest) contraction of the preparation, but considerably enhanced the increase in amplitude of contractions in a rhythmic series (positive “Bowditch's ladder”). The higher the frequency of stimulation (between 1 and 5 Hz) of the preparation, the stronger the positive inotropic effect of histamine and egg albumin. Inactivation of fast Na channels by depolarization of the membrane of the myocardial cells in medium with a high potassium concentration (13.7 mM KCl) did not abolish these effects of histamine and the antigen. Conversely these effects were completely suppressed by blocking of the slow Na, Ca channels by compound D-600 (1\10−6 g/ml).

Changes in contractile activity of the rabbit myocardium as a result of burn shock of varied duration

Experiments were carried out on papillary muscles isolated from the rabbit heart 10, 60, or 180 min after thermal injury to the animal. Isometric contractions were recorded during stimulation of the preparation at changing frequencies (within the range from 0.1 to 2 Hz) and during poststimulation potentiation. The degree of disturbance of myocardial contractility as a result of burns was found to increase with an increase in the duration of burn shock: In all the papillary muscles isolated 3 h after burning and in 50% of those isolated 1 h after burning the “biphasic” frequency-strength (f-P) relationship characteristic of the normal myocardium was converted into “monophasic” (the amplitude of the contractions decreased progressively with an increase in frequency) and poststimulation potentiation, normally absent, appeared. After shock lasting 10 min, poststimulation potentiation was observed only in some preparations and no change in f-P was present. The normal inotropic relationships of the myocardial rhythm were restored after a twofold increase in [Ca++]0 or after prolonged (3–4 h) perfusion of the preparation with normal Tyrode solution. Changes in inotropic relationships of the myocardial rhythm in burn shock were similar to the changes in f-P observed after blockade of the calcium channels with compound D-600.

Changes in contractile activity of the rabbit myocardium in burn shock

In vitro experiments on the papillary muscles of the rabbit heart showed that 1 h after burn trauma myocardial contractility is disturbed in 50% of cases. It is concluded that this may be one cause of the severe disturbance of cardiac output observed in the same experiments.

Interdigestive motor activity of Heidenhain pouches in relation to main stomach in conscious dogs.

A great number of studies using Heidenhain pouches have been reported, but most of them have been concerned with secretory activity. Studies on the motor activity of the pouch are few, and our knowledge about it is rather limited. In the present study, therefore, long-term changes in contractile activity of the Heidenhain pouches were recorded simultaneously with those of the main stomach in conscious dogs by means of chronically implanted force transducers. It was found that during the interdigestive state Heidenhain pouches contracted precisely in association with the main stomach. During this time a series of strong contractions arose simultaneously in the Heidenhain pouch and the main stomach, lasted for 24.2 +/- 1.90 min, and then ceased abruptly. Such strong contractions were followed by a long period of motor quiescence lasting for 86.9 +/- 6.06 min. These characteristic recurring episodes in the Heidenhain pouch and the main stomach lasted during the interdigestive state but were inhibited by the ingestion of food or intravenous administration of pentagastrin. These findings indicate that the interdigestive motor activity of the stomach is strongly controlled by a humoral factor(s) rather than the parasympathetic nervous system; however, we also propose a possible role for the sympathetic nervous system for coordinated occurrence of the interdigestive contractions between the Heidenhain pouch and the main stomach.

THE MOTILITY OF THE LOWER ESOPHAGEAL SPHINCTER

Changes in lower esophageal sphincter (LES) motility have been mainly studied by intraluminal manometry. However, it is not suitable for continuous measurement of LES pressure. With extraluminal force transducers developed and constracted in our laboratory, we measured changes in contractile activity of the LES. Three anesthetized mongrel dogs were used for preliminary experiment. A transducer was sutured on the serosal surface of the LES immediately inferior to the phrenoesophageal membrane. A catheter with a side hole was simultaneously passed into the stomach through a mouth so that the side hole was anchored at the highest pressure zone of the gastroesophageal junction. It was found that dose-related changes in motor activity of the LES to pentagastrin were obtained by both methods. This result indicate changes obtained by transducers represent those in intraluminal pressure measured manometory. Transducers were chronically implanted on the LES and the gastric body and antrum to record changes in contractile activity in conscious state. It was found that a group of contractions lasting for 25 +/- 2.5 min occurred at regular intervals of quiescence until next meal. Furthermore, these motor increase precisely coincided with the interdigestive contractions of the stomach.

Maximal rate of the left ventricular pressure fall (peak negative dP/dt) in early stage of myocardial ischemia following experimental coronary occlusion.

Short-term, repeated myocardial ischemia was produced in 20 opened-chest anesthetized dogs by left anterior descending (LAD) branch occlusion. Left ventricular pressure (LVP) and its dP/dt were recorded by Satham SF-1 transducer, and isometric local force (F) was measured by a Walton-Brodie strain gauge arch sewn onto LV free wall. In all experiments, within a few beats after LAD occlusion, peak negative dP/dt started to diminish its amplitude, reaching a nadir after 20-30 sec (63 +/- 5% of control, 9 dogs). It recovered to 83 +/- 3% of control level in 45 sec and remained essentially unchanged thereafter. This change preceded those of LVP and max dP/dt, which showed only minor falls. In 6 dogs, changes by occluding root of LAD were compared with those by its branch occlusion. The greater the extent of ischemia, the more marked and prolonged were the changes. While F in the ischemic center (Fc) rapidly lost its contractile activity following LAD occlusion, F in marginal zone between infarcted and non-infarcted region (Fm) showed variable extent and different time-course of its diminution. Thus, it was concluded that the change in peak negative dP/dt following LAD occlusion was one of the sensitive signs of early ischemic changes, and was attributed at least in part to characteristic changes in contractile activity of myocardium surrounding the ischemic injury.

Effects of glycerol treatment on contractility and transmembrane potentials in cardiac tissue

Recordings were made of transmembrane potentials and contractile activity before, during, and after treatment of guinea-pig left atria with Tyrode's solution made hypertonic with 400 m m-glycerol. During treatment with glycerol solution developed tension declined to a steady level while rest tension and transmembrane potentials were unchanged. After return to non-glycerol Tyrode's rest tension increased and developed tension declined further, sometimes to zero resulting in a period of quiescence. With time rest tension declined and developed tension increased, eventually returning to control values. Depolarization of transmembrane rest potentials was shown to accompany the decline of tension after return to non-glycerol Tyrode's. Field stimulation did not prevent these changes. However, if the tissue was placed in 400 m m-sucrose Tyrode's after treatment with 400 m m-glycerol solution, developed tension did not decline at all. In addition, it was shown that increased calcium or magnesium concentration prevents the decline in developed tension as well as depolarization of resting potentials after return to non-glycerol Tyrode's. It was also shown that similar changes in contractile activity occur after glycerol treatment of dog atrial tissue. However, glycerol treatment of frog cardiac tissue has little effect.

Rabbit uterine contractile activity increase following coitus

Rabbit uterine contractile activity changes following coitus were monitored with extraluminal contractile force transducers (ECFT's). Circular muscle contractile activity (but not that of longitudinal) initially increased following coitus. Subsequent increases in contractile force and frequency were recorded from both myometrial layers but for a longer period from longitudinal muscle than from circular muscle.