Biomedical subjects

V R Pratusevich

Publications and source records attributed to V R Pratusevich.

9 recordsLinked to original sources

PubMed2001

Relationship between myosin phosphorylation and contractile capability of canine airway smooth muscle.

To better understand excitation-contraction coupling in smooth muscle, myosin phosphorylation and force-velocity properties of canine tracheal muscle were compared during the rise and early plateau of force in electrically stimulated tetani. Velocity reached a peak of approximately 1.5 times plateau value when force had risen to approximately 45% of its maximum value and then declined progressively. Except early in the tetanus, when phosphorylation rose rapidly, maximum power and phosphorylation had nearly parallel time courses, reaching peaks of 1.2-1.3 times reference at 6-8 s before declining to the plateau level at approximately 12 s. Force, velocity, maximum power, and phosphorylation fell somewhat during the plateau, with the closest correlation between phosphorylation and power. These results suggest that 1) early velocity slowing is not associated with light chain dephosphorylation and 2) maximum power, which we use to signal changes in activation, is closely correlated with the degree of light chain phosphorylation, at least when phosphorylation level is not changing rapidly. Dissociation of these two properties would be expected early in the tetanus if phosphorylation precedes mechanical activity.

Animals↗

PubMed2000

Series-to-parallel transition in the filament lattice of airway smooth muscle.

Force-velocity curves measured at different times during tetani of sheep trachealis muscle were analyzed to assess whether velocity slowing could be explained by thick-filament lengthening. Such lengthening increases force by placing more cross bridges in parallel on longer filaments and decreases velocity by reducing the number of filaments spanning muscle length. From 2 s after the onset of stimulation, when force had achieved 42% of it final value, to 28 s, when force had been at its tetanic plateau for approximately 15 s, velocity decreases were exactly matched by force increases when force was adjusted for changes in activation, as assessed from the maximum power value in the force-velocity curves. A twofold change in velocity could be quantitatively explained by a series-to-parallel change in the filament lattice without any need to postulate a change in cross-bridge cycling rate.

Actin Cytoskeleton↗

PubMed1996

Factors shaping the confocal image of the calcium spark in cardiac muscle cells.

The interpretation of confocal line-scan images of local [Ca2+]i transients (such as Ca2+ sparks in cardiac muscle) is complicated by uncertainties in the position of the origin of the Ca2+ spark (relative to the scan line) and by the dynamics of Ca(2+)-dye interactions. An investigation of the effects of these complications modeled the release, diffusion, binding, and uptake of Ca2+ in cardiac cells (producing a theoretical Ca2+ spark) and image formation in a confocal microscope (after measurement of its point-spread function) and simulated line-scan images of a theoretical Ca2+ spark (when it was viewed from all possible positions relative to the scan line). In line-scan images, Ca2+ sparks that arose in a different optical section or with the site of origin displaced laterally from the scan line appeared attenuated, whereas their rise times slowed down only slightly. These results indicate that even if all Ca2+ sparks are perfectly identical events, except for their site of origin, there will be an apparent variation in the amplitude and other characteristics of Ca2+ sparks as measured from confocal line-scan images. The frequency distributions of the kinetic parameters (i.e., peak amplitude, rise time, fall time) of Ca2+ sparks were calculated for repetitive registration of stereotyped Ca2+ sparks in two experimental situations: 1) random position of the scan line relative to possible SR Ca(2+)-release sites and 2) fixed position of the scan line going through a set of possible SR Ca(2+)-release sites. The effects of noise were incorporated into the model, and a visibility function was proposed to account for the subjective factors that may be involved in the evaluation of Ca(2+)-spark image parameters from noisy experimental recordings. The mean value of the resulting amplitude distributions underestimates the brightness of in-focus Ca2+ sparks because large numbers of out-of-focus Ca2+ sparks are detected (as small Ca2+ sparks). The distribution of peak amplitudes may split into more than one subpopulation even when one is viewing stereotyped Ca2+ sparks because of the discrete locations of possible SR Ca(2+)-release sites in mammalian ventricular heart cells.

Animals↗

PubMed1995

Plasticity in canine airway smooth muscle.

The large volume changes of some hollow viscera require a greater length range for the smooth muscle of their walls than can be accommodated by a fixed array of sliding filaments. A possible explanation is that smooth muscles adapt to length changes by forming variable numbers of contractile units in series. To test for such plasticity we examined the muscle length dependence of shortening velocity and compliance, both of which will vary directly with the number of thick filaments in series. Dog tracheal smooth muscle was studied because its cells are arrayed in long, straight, parallel bundles that span the length of the preparation. In experiments where muscle length was changed, both compliance and velocity showed a strong dependence on muscle length, varying by 1.7-fold and 2.2-fold, respectively, over a threefold range of length. The variation in isometric force was substantially less, ranging from a 1.2- to 1.3-fold in two series of experiments where length was varied by twofold to an insignificant 4% variation in a third series where a threefold length range was studied. Tetanic force was below its steady level after both stretches and releases, and increased to a steady level with 5-6 tetani at 5 min intervals. These results suggest strongly that the number of contractile units in series varies directly with the adapted muscle length. Temporary force depression after a length change would occur if the change transiently moved the filaments from their optimum overlap. The relative length independence of the adapted force is explained by the reforming of the filament lattice to produce optimum force development, with commensurate changes of velocity and compliance.

Adaptation, Physiological↗

PubMed1994

Plasticity in smooth muscle, a hypothesis.

The controversial finding that the thick filaments of smooth muscle can be evanescent leads to the hypothesis that the large functional range of this muscle is accommodated by plastic rearrangements that place more thick filaments in series at longer lengths. Our preliminary finding that the shortening velocity and compliance of dog tracheal muscle were strongly dependent on adapted muscle length, while force was much less length dependent, supports this hypothesis (V.R. Pratusevich, C.Y. Seow, and L.E. Ford. Biophys. J. 66: A139, 1994). The hypothesis leads to two further corollaries. The first is that the lengthening of the thick filaments that must accompany their reformation will cause a series to parallel transition: fewer long filaments span the muscle length, but the longer filaments have more cross bridges acting in parallel. The second is that there is more than one activating mechanism in smooth muscle. It is known that myosin light chain phosphorylation activates the actomyosin ATPase, but this same phosphorylation also causes a structural change that facilitates filament formation. The consideration that the unaggregated, phosphorylated myosin must be prevented from competing with myosin in thick filaments and hydrolyzing ATP suggests that there must be a second mechanism that must allow the thin filaments to interact selectively with filamentous myosin. This need for a second activating mechanism may explain the presence of tropomyosin, calponin, and caldesmon on thin filaments. Although the two corollaries follow from the initial hypothesis, it should be emphasized that the three are not mutually dependent, and that the proof or disproof of any one of them would not prove or disprove the others.

Animals↗

PubMed1992

Force-frequency relations in hypertrophic heart muscle: a mathematical model for excitation-contraction coupling.

Static and dynamic chrono-inotropic responses were recorded from both normal and hypertrophic rat auricular myocardium. The slope of the static force-frequency relation for hypertrophic hearts was steeper than that for control hearts. Computer experiments were designed to study the cellular mechanisms underlying the changes in the force-frequency response associated with heart hypertrophy, with the aid of a mathematical model for excitation-contraction coupling in rat heart. A set of equations was derived which permitted to study the effects on the chronoinotropic relations of both the geometrical dimensions of cardiomyocytes and the sarcoplasmic reticulum, and of the variation in activity of mechanisms for Ca movements through the sarcolemma and the sarcoreticular membrane. A comparison of data obtained from simulated and real experiments suggested that the features characteristic of force-frequency relations for hypertrophic heart are a result of an enhanced volume of intracellular Ca-stores rather than of the total volume of the cardiomyocyte.

Animals↗

PubMed1991

[The dependence of rhythmic myocardial inotropism on the degree of stretching].

The length-dependence of force-frequency relations in rat heart was studied in isometrically contracting papillary muscles. Negative force-frequency relations were observed for all lengths; the slope of the optimal length curve (Lopt) corresponding to peak contractile force during rhythmic pacing at 0.5 Hz, was greater than that for both 0.7 Lopt and 1.20 Lopt. The slope of static force-frequency curve was estimated at various muscle lengths in the range between 70 and 120% of Lopt. It was concluded that: 1) the heart muscle length corresponding to the maximal peak contractile force depends on stimulation frequency; 2) the slope of the force-frequency curve is maximal at the muscle length of 90 to 95% optimal length determined at basis stimulation frequency (0.5 Hz). The operating point for heart muscle in vivo is believed to be biased from the maximum of length-tension curve to its ascending part.

Animals↗

PubMedDate not supplied

[Chronoinotropic reaction of the hypertrophied myocardium using an electromechanical coupling mathematical model].

Static and dynamic chrono-inotropic responses were recorded from both normal and hypertrophic rat auricular myocardium. The slope of the static force-frequency relation from hypertrophied heart was steeper than in the control hearts. The cellular mechanisms underlying changes in the force frequency response associated with hypertrophy of the heart were studied by means of a mathematical model of excitation-contraction coupling. The characteristic features of hypertrophied heart force-frequency relations are shown to be due to the enhanced volume of the intracellular Ca-stores in contrast to the total volume of the cardiomyocyte.

Animals↗

PubMedDate not supplied

[Evaluation of the effect of cardiotropic agents using a mathematical model of electromechanical coupling].

An assessment of the ionic action mechanism of cardiotropic substances with the aid of a mathematical model for excitation-contraction coupling in myocardium is proved to be possible. The technique developed consists in the model parameter identification from the experimental data on electrical and mechanical activity of myocardial strip. The validity of the technique is tested using the known mechanism drugs. An example is given of analysis by the technique suggested of the action mechanism of diltiazem on the rat papillary muscle.

Animals↗