Inhibition by theophylline of the early component of canine ventricular contraction

1982 ◽  
Vol 242 (3) ◽  
pp. H349-H358
Author(s):  
M. Endoh ◽  
T. Iijima ◽  
S. Motomura
Keyword(s):  
Mechanical Characteristics ◽  
Calcium Influx ◽  
Myocardial Cell ◽  
Ventricular Muscle ◽  
Late Component ◽  
Ventricular Contraction ◽  
Early Component ◽  
Peak Tension ◽  
Time To Peak ◽  
Plateau Potential

Changes in mechanical characteristics of the isolated canine ventricular muscle were investigated during interaction of isoproterenol with theophylline or caffeine. An early and a late component with time to peak tension of 80 and 150 ms, respectively, were differentiated in a single contraction of the muscle stimulated at 0.5 Hz at 37 degrees C during the interaction of isoproterenol and theophylline, or isoproterenol and caffeine. Isoproterenol increased preferentially the early component and affected only slightly the late one. Theophylline or caffeine elevated the early component less than the late one. In the presence of theophylline + isoproterenol or caffeine + isoproterenol the peak tension was achieved by a late component, whereas the increase in the early one induced by isoproterenol in 3 X 10(-7) M and higher was depressed significantly. During the interaction the rate of twitch relaxation was accelerated further rather than depressed. Changes in action potential indicate that the calcium influx via the myocardial cell membrane during depolarization was increased: the peak plateau potential was significantly elevated by theophylline alone and further by theophylline + isoproterenol. These results indicate that theophylline and caffeine (2 mM) may act intracellularly to inhibit the isoproterenol-induced promotion of the early component without impairing the isoproterenol-induced acceleration of relaxation in the canine ventricular muscle.

Effect of rate changes on strength and time course of contraction of papillary muscle

1963 ◽  
Vol 204 (3) ◽  
pp. 451-457 ◽  
Author(s):  
Jan Koch-Weser
Keyword(s):  
Entire Range ◽  
Maximum Rate ◽  
Time Course ◽  
Normal Development ◽  
Papillary Muscles ◽  
Ventricular Muscle ◽  
High Frequencies ◽  
Peak Tension ◽  
Time To Peak ◽  
Opposing Effect

The influence of 14 frequencies of contraction (between 0.2 and 300 beats/min) on the development of tension and on the time course of contraction was determined in 40 isometrically contracting, isolated cat papillary muscles at 38 C. Only cylindrical muscles with radius <0.43 mm were included, since this was found to be the maximum thickness compatible with normal development of tension at high frequencies. Increases in frequency were associated over the entire range with decreases in the time to peak tension (total 40%) and in the relaxation time (total 49%), and increases in the maximum rate of development of tension (total 560%) and in the peak tension developed (total 340%). These findings indicate that changes in heart rate alter both the degree of activation of the contractile elements and the duration of their active state. It is concluded that the opposing effect of both of these changes must be considered in any analysis of the influence of alterations in rate or rhythm of the heart on the strength of contraction of mammalian ventricular muscle.

Inhibition of rest potentiation in canine ventricular muscle by BAY K 8644: comparison with caffeine

1989 ◽  
Vol 257 (2) ◽  
pp. H399-H406
Author(s):  
L. V. Hryshko ◽  
R. Bouchard ◽  
T. Chau ◽  
D. Bose
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Calcium Uptake ◽  
Calcium Influx ◽  
Bay K 8644 ◽  
Contractile Apparatus ◽  
Peak Tension ◽  
Time To Peak ◽  
Configuration Changes ◽  
Action Potential Configuration

Rest potentiation, believed to be due to increased utilization of sarcoplasmic reticular calcium, was converted to rest depression by BAY K 8644 (1 microM). Plateau height and duration of the postrest beat were enhanced by BAY K 8644, suggesting an enhancement of extracellular calcium entry. Caffeine (3 mM) also produced depression at all rest intervals, although to a lesser extent than BAY K 8644. Compared with BAY K 8644, treatment with caffeine resulted in an elevation of plateau amplitude and a shortening of action potential duration. Action potential configuration changes induced by rest were unaltered by caffeine despite reduction in rest potentiation. Caffeine-induced rest depression was associated with an increase in the time to peak tension. This was not observed with BAY K 8644. Treatment with both caffeine (3 mM) and BAY K 8644 (1 microM) greatly prolonged time to peak tension. Action potential duration and plateau height were either maintained or increased. Less rest depression was observed with the combination than with either agent alone. These results suggest that 1) BAY K 8644 and caffeine inhibit rest potentiation by different mechanisms, and 2) caffeine-induced inhibition of calcium uptake by the sarcoplasmic reticulum may enhance the effect of BAY K 8644-induced increase in calcium influx on the contractile apparatus.

Calcium fluxes and contractility in isolated guinea pig atrium: effect of A23187

1978 ◽  
Vol 235 (1) ◽  
pp. C13-C19 ◽  
Author(s):  
D. R. Holland ◽  
W. M. Armstrong ◽  
M. I. Steinberg
Keyword(s):  
Guinea Pig ◽  
Myocardial Cell ◽  
Ionophore A23187 ◽  
Inotropic Action ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Endogenous Histamine ◽  
Resultant Increase ◽  
45Ca Efflux

The Ca2+ ionophore A23187 (10(-6) to 3 X 10(-5) M) increased the force of contraction is isolated guinea pig atria. In individual twitches, peak tension, maximum rate of tension development, time to peak tension, and total twitch duration were all increased by A23187. Tripelennamine, indomethacin, and atropine did not significantly alter the inotropic effect of A23187. Serotonin produced changes in individual twitches that differed qualitatively and quantitatively from those of A23187. Therefore, the inotropic action of A23187 is probably not mediated by release of endogenous histamine, prostaglandins, acetylcholine, or serotonin. 45Ca influx and efflux were increased by A23187. The enhanced 45Ca efflux exceeded that which would be predicted if the ionophore acted only to increase the passive Ca2+ permeability of the myocardial cell membrane. These results suggest that A23187 facilitates the entry of extracellular Ca2+ into the myocardial cell and the release of intracellular Ca2+ stores into the myoplasm. The resultant increase in intracellular Ca2+ activity could account for the positive inotropic action of A23187.

scholarly journals Alpha and beta myosin isoforms and human atrial and ventricular contraction

2021 ◽  
Author(s):  
Jonathan Walklate ◽  
Cecilia Ferrantini ◽  
Chloe A. Johnson ◽  
Chiara Tesi ◽  
Corrado Poggesi ◽  
...  
Keyword(s):  
Mechanical Characteristics ◽  
Essential Feature ◽  
Myosin Isoforms ◽  
Cardiac Myosin ◽  
Ventricular Contraction ◽  
Functional Characteristics

AbstractHuman atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly β-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & β-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils. This allows us to consider the extent to which the atrial vs ventricular mechanical characteristics are defined by the myosin isoform expressed, and how the isoform properties are matched to their physiological roles. To do this we Outline the essential feature of atrial and ventricular contraction; Explore the molecular structural and functional characteristics of the two myosin isoforms; Describe the contractile behaviour of myocytes and myofibrils expressing a single myosin isoform; Finally we outline the outstanding problems in defining the differences between the atria and ventricles. This allowed us consider what features of contraction can and cannot be ascribed to the myosin isoforms present in the atria and ventricles.

Characteristics of the second inward current in cells isolated from rat ventricular muscle

1983 ◽  
Vol 219 (1217) ◽  
pp. 447-469 ◽  
Keyword(s):  
Single Cells ◽  
External Solution ◽  
Maximum Level ◽  
Charge Carriers ◽  
Ventricular Muscle ◽  
Inward Current ◽  
Adult Rat ◽  
Time To Peak ◽  
Rat Hearts ◽  
Steady Level

The second inward current ( I si ) in single cells isolated from ventricular muscle of adult rat hearts was measured in response to step depolarizations under voltage-clamp conditions. The major ion carrying this current was Ca, and I si was reduced or abolished by Mn, Ni, Cd, nifedipine, nimodipine and D600. Sr and Ba could substitute for Ca as charge carriers, and reduced the rate of apparent inactivation of I si . These effects of Sr and Ba, together with the relation between the steady level of apparent inactivation and membrane potential in Ca containing solution, were taken as evidence that inactivation was at least in part dependent on internal Ca. The reduction of external Na to 11% of normal caused a reduction in peak I si when Ca was present in the external solution, but did not reduce I si when Ca was replaced by Sr. It therefore seems unlikely that Na is a major charge carrier I si under the conditions of our experiments. The time-to-peak and rate of apparent inactivation of I si were faster than in previous studies that used multicellular preparations. Both the kinetics and peak amplitude of I si were markedly dependent on temperature ( Q 10 close to 3). Contraction of the cells, which was monitored optically, was initiated within 3 ms of the peak I si , reached a maximum level after approximately 40–50 ms, and was about 100 ms in duration.

Abnormal contraction caused by expression of Gi-coupled receptor in transgenic model of dilated cardiomyopathy

2001 ◽  
Vol 280 (4) ◽  
pp. H1653-H1659 ◽  
Author(s):  
Anthony J. Baker ◽  
Charles H. Redfern ◽  
Mark D. Harwood ◽  
Paul C. Simpson ◽  
Bruce R. Conklin
Keyword(s):  
Transgenic Mice ◽  
Right Ventricular ◽  
Dilated Cardiomyopathy ◽  
Myocardial Function ◽  
Expression System ◽  
Contractile Force ◽  
Ventricular Muscle ◽  
Time To Peak ◽  
Contraction And Relaxation

Although increased Gi signaling has been associated with dilated cardiomyopathy in humans, its role is not clear. Our goal was to determine the effects of chronically increased Gi signaling on myocardial function. We studied transgenic mice that expressed a Gi-coupled receptor (Ro1) that was targeted to the heart and regulated by a tetracycline-controlled expression system. Ro1 expression for 8 wk resulted in abnormal contractions of right ventricular muscle strips in vitro. Ro1 expression reduced myocardial force by >60% (from 35 ± 3 to 13 ± 2 mN/mm2, P < 0.001). Nevertheless, sensitivity to extracellular Ca2+ was enhanced. The extracellular [Ca2+] resulting in half-maximal force was lower with Ro1 expression compared with control (0.41 ± 0.05 vs. 0.88 ± 0.05 mM, P < 0.001). Ro1 expression slowed both contraction and relaxation kinetics, increasing the twitch time to peak (143 ± 6 vs. 100 ± 4 ms in control, P < 0.001) and the time to half relaxation (124 ± 6 vs. 75 ± 6 ms in control, P < 0.001). Increased pacing frequency increased contractile force threefold in control myocardium ( P < 0.001) but caused no increase of force in Ro1-expressing myocardium. When stimulation was interrupted with rests, postrest force increased in control myocardium, but there was postrest decay of force in Ro1-expressing myocardium. These results suggest that defects in contractility mediated by Gi signaling may contribute to the development of dilated cardiomyopathy.

Effect of hypoxia on mechanical function in the neonatal mammalian heart

1978 ◽  
Vol 235 (5) ◽  
pp. H469-H474 ◽  
Author(s):  
J. M. Jarmakani ◽  
M. Nakazawa ◽  
T. Nagatomo ◽  
G. A. Langer
Keyword(s):  
Glycolytic Pathway ◽  
Mechanical Function ◽  
Maximal Rate ◽  
Half Time ◽  
Perfusion Rate ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Newborn Rabbit ◽  
Mammalian Heart

The effect of 30 min of hypoxia followed by reoxygenation on mechanical function was studied in isolated, arterially perfused, neonatal rabbit and dog hearts. All studies were performed at a perfusion rate of 2.5 ml/g-min, at a pacing rate of 60 beats/min and at 27 degrees C. The muscles were perfused with Krebs-Henseleit solutions equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia). In the newborn rabbit and dog, both the developed tension (DT) and the maximal rate of tension development (dT/dtmax+) decreased during the first 3 min of hypoxia and then recovered to values not different from control. The effect of hypoxia on DT and dT/dtmax+ was inversely related to age in both the rabbit and dog. The equations describing the decline in DT and dT/dTmax+ during hypoxia and the recovery during reoxygenation were best expressed by two or three exponentials. Time to peak tension and half time to relaxation decreased during hypoxia and the decrease was also inversely related to age. The fact that the newborn was able to maintain normal mechanical function during hypoxia suggests that the newborn is capable of maintaining normal myocardial ATP levels due to enhanced flux through the glycolytic pathway.

Enhanced contractility during relaxation of cat papillary muscle

1975 ◽  
Vol 228 (6) ◽  
pp. 1708-1716 ◽  
Author(s):  
BG Bass
Keyword(s):  
Papillary Muscle ◽  
Time Course ◽  
Isometric Tension ◽  
Contractile Element ◽  
Cat Papillary Muscle ◽  
Postextrasystolic Potentiation ◽  
Peak Tension ◽  
Time To Peak ◽  
In Series ◽  
Antecedent Control

Contractility during relaxation of isometric tension was studied in isolated, electrically driven cat papillary muscle by interpolation of test extrasystoles, all of whichpartially fused with their antecedent (control) contractions, were separated by computer from the fused contractions and then analyzed. The time course of the restitutionof contractility during relaxation was defined by plotting maximal positive dT/dt andtime-to-peak tension of the computer-separated extrasystole versus delay preceding the extrasystole. The dT/dt and time-to-peak tension, which steadily decline with progressive prematurity between contractions, both increase again during late relaxation, become progressively greater still earlier in relaxation, peak shortly after peak isometric tension, and then again decline. This phase of an apparently enhanced contractilityduring relaxation is depressed in low Ca'++ and is transmitted into the postextrasystolic period (in which it is superimposed on the usual postextrasystolic potentiation). The possible contributions of variations in series-elastic component and contractile-element lengths, actionpotential characteristics, and other factors on contractility during relaxation are discussed. It is suggested that enhanced contractility during relaxation may also be related in part to the decay of the intracellular free Ca'++ transient.

Two Types of Voltage-Gated K+ Currents in Dissociated Heart Ventricular Muscle Cells of the Snail Lymnaea stagnalis

1999 ◽  
Vol 82 (5) ◽  
pp. 2415-2427 ◽  
Author(s):  
M. S. Yeoman ◽  
P. R. Benjamin
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Muscle Cells ◽  
Delayed Rectifier ◽  
Voltage Sensitivity ◽  
Ventricular Muscle ◽  
Current Time ◽  
Voltage Gated ◽  
Time To Peak ◽  
Voltage Dependent

We have used a combination of current-clamp and voltage-clamp techniques to characterize the electrophysiological properties of enzymatically dissociated Lymnaea heart ventricle cells. Dissociated ventricular muscle cells had average resting membrane potentials of −55 ± 5 mV. When hyperpolarized to potentials between −70 and −63 mV, ventricle cells were capable of firing repetitive action potentials (8.5 ± 1.2 spikes/min) that failed to overshoot 0 mV. The action potentials were either simple spikes or more complex spike/plateau events. The latter were always accompanied by strong contractions of the muscle cell. The waveform of the action potentials were shown to be dependent on the presence of extracellular Ca2+ and K+ ions. With the use of the single-electrode voltage-clamp technique, two types of voltage-gated K+ currents were identified that could be separated by differences in their voltage sensitivity and time-dependent kinetics. The first current activated between −50 and −40 mV. It was relatively fast to activate (time-to-peak; 13.7 ± 0.7 ms at +40 mV) and inactivated by 53.3 ± 4.9% during a maintained 200-ms depolarization. It was fully available for activation below −80 mV and was completely inactivated by holding potentials more positive than −40 mV. It was completely blocked by 5 mM 4-aminopyridine (4-AP) and by concentrations of tetraethylammonium chloride (TEA) >10 mM. These properties characterize this current as a member of the A-type family of voltage-dependent K+ currents. The second voltage-gated K+ current activated at more depolarized potentials (−30 to −20 mV). It activated slower than the A-type current (time-to-peak; 74.1 ± 3.9 ms at +40 mV) and showed little inactivation (6.2 ± 2.1%) during a maintained 200-ms depolarization. The current was fully available for activation below −80 mV with a proportion of the current still available for activation at potentials as positive as 0 mV. The current was completely blocked by 1–3 mM TEA. These properties characterize this current as a member of the delayed rectifier family of voltage-dependent K+ currents. The slow activation rates and relatively depolarized activation thresholds of the two K+ currents are suggestive that their main role is to contribute to the repolarization phase of the action potential.

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