Biomedical subjects

Lawrence C Rome

Publications and source records attributed to Lawrence C Rome.

8 recordsLinked to original sources

PubMed2006

Design and function of superfast muscles: new insights into the physiology of skeletal muscle.

Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.

Air Sacs↗

PubMed2005

Generating electricity while walking with loads.

We have developed the suspended-load backpack, which converts mechanical energy from the vertical movement of carried loads (weighing 20 to 38 kilograms) to electricity during normal walking [generating up to 7.4 watts, or a 300-fold increase over previous shoe devices (20 milliwatts)]. Unexpectedly, little extra metabolic energy (as compared to that expended carrying a rigid backpack) is required during electricity generation. This is probably due to a compensatory change in gait or loading regime, which reduces the metabolic power required for walking. This electricity generation can help give field scientists, explorers, and disaster-relief workers freedom from the heavy weight of replacement batteries and thereby extend their ability to operate in remote areas.

Bioelectric Energy Sources↗

PubMed2005

Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm.

We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1; P < 0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms (P < 0.01), and a 19% increase (P < 0.05) in fibers expressing only the slow SERCA isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on diaphragm homogenates indicated that COPD diaphragms expressed only one-third the SERCA1 content noted in control diaphragms; in contrast, COPD and control diaphragms did not differ with respect to SERCA2 content. The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data (Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB. Am J Respir Crit Care Med 168: 706-713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm.

Calcium-Transporting ATPases↗

PubMed2003

Human diaphragm remodeling associated with chronic obstructive pulmonary disease: clinical implications.

Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.

Adaptation, Physiological↗

PubMed2003

Cross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers.

Because the major processes involved in muscle contraction require rapid utilization of ATP, measurement of ATP utilization can provide important insights into the mechanisms of contraction. It is necessary, however, to differentiate between the contribution made by cross-bridges and that of the sarcoplasmic reticulum (SR) Ca2+ pumps. Specific and potent SR Ca2+ pump blockers have been used in skinned fibers to permit direct measurement of cross-bridge ATP utilization. Up to now, there was no analogous cross-bridge blocker. Recently, N-benzyl-p-toluene sulfonamide (BTS) was found to suppress force generation at micromolar concentrations. We tested whether BTS could be used to block cross-bridge ATP utilization, thereby permitting direct measurement of SR Ca2+ pump ATP utilization in saponin-skinned fibers. At 25 microM, BTS virtually eliminates force and cross-bridge ATP utilization (both <4% of control value). By taking advantage of the toadfish swimbladder muscle's unique right shift in its force-Ca2+ concentration ([Ca2+]) relationship, we measured SR Ca2+ pump ATP utilization in the presence and absence of BTS. At 25 microM, BTS had no effect on SR pump ATP utilization. Hence, we used BTS to make some of the first direct measurements of ATP utilization of intact SR over a physiological range of [Ca2+]at 15 degrees C. Curve fits to SR Ca2+ pump ATP utilization vs. pCa indicate that they have much lower Hill coefficients (1.49) than that describing cross-bridge force generation vs. pCa (approximately 5). Furthermore, we found that BTS also effectively eliminates force generation in bundles of intact swimbladder muscle, suggesting that it will be an important tool for studying integrated SR function during normal motor behavior.

Adenosine Triphosphate↗

PubMed2002

The design of vertebrate muscular systems: comparative and integrative approaches.

For more than 50 years, it has been known that vertebrates engage in a wide range of motor activities and that they possess muscle types with a similarly large range of contractile properties. However, only during the past 15 years has it been shown experimentally that the contractile properties of muscle fibers are well adjusted to their in vivo function. Arriving at this conclusion has required an integrative approach, that is, comparing measurements of muscle fiber properties with measurements of fiber use during normal motor activity. Because the muscles of mammals (and humans) generally are heterogenous in fiber type, this makes it technically very difficult to measure either the contractile properties of different fiber types or their use during normal motor activity. Therefore, many of the advances in the understanding of the design and function of vertebrate muscular systems have come from work on lower vertebrates. Fish, because of the anatomic separation of different muscle fiber types, have provided a key experimental model on which much of what is known about muscle design has been determined. Frogs, because of the near homogeneity of their large extensor muscles used during jumping, also provide an important model which will, in the near future, serve as the first platform where molecular properties of muscle (calcium and cross-bridge kinetics) can be related to whole body movement in a meaningful and predictive manner.

Animals↗

PubMed2002

Jumping in frogs: assessing the design of the skeletal system by anatomically realistic modeling and forward dynamic simulation.

Comparative musculoskeletal modeling represents a tool to understand better how motor system parameters are fine-tuned for specific behaviors. Frog jumping is a behavior in which the physical properties of the body and musculotendon actuators may have evolved specifically to extend the limits of performance. Little is known about how the joints of the frog contribute to and limit jumping performance. To address these issues, we developed a skeletal model of the frog Rana pipiens that contained realistic bones, joints and body-segment properties. We performed forward dynamic simulations of jumping to determine the minimal number of joint degrees of freedom required to produce maximal-distance jumps and to produce jumps of varied take-off angles. The forward dynamics of the models was driven with joint torque patterns determined from inverse dynamic analysis of jumping in experimental frogs. When the joints were constrained to rotate in the extension-flexion plane, the simulations produced short jumps with a fixed angle of take-off. We found that, to produce maximal-distance jumping, the skeletal system of the frog must minimally include a gimbal joint at the hip (three rotational degrees of freedom), a universal Hooke's joint at the knee (two rotational degrees of freedom) and pin joints at the ankle, tarsometatarsal, metatarsophalangeal and iliosacral joints (one rotational degree of freedom). One of the knee degrees of freedom represented a unique kinematic mechanism (internal rotation about the long axis of the tibiofibula) and played a crucial role in bringing the feet under the body so that maximal jump distances could be attained. Finally, the out-of-plane degrees of freedom were found to be essential to enable the frog to alter the angle of take-off and thereby permit flexible neuromotor control. The results of this study form a foundation upon which additional model subsystems (e.g. musculotendon and neural) can be added to test the integrative action of the neuromusculoskeletal system during frog jumping.

Animals↗

PubMed2002

Functional morphology of proximal hindlimb muscles in the frog Rana pipiens.

Musculoskeletal models have become important tools in understanding motor control issues ranging from how muscles power movement to how sensory feedback supports movements. In the present study, we developed the initial musculotendon subsystem of a realistic model of the frog Rana pipiens. We measured the anatomical properties of 13 proximal muscles in the frog hindlimb and incorporated these measurements into a set of musculotendon actuators. We examined whether the interaction between this musculotendon subsystem and a previously developed skeleton/joint subsystem captured the passive behavior of the real frog's musculoskeletal system. To do this, we compared the moment arms of musculotendon complexes measured experimentally with moment arms predicted by the model. We also compared sarcomere lengths measured experimentally at the starting and take-off positions of a jump with sarcomere lengths predicted by the model at these same limb positions. On the basis of the good fit of the experimental data, we used the model to describe the multi-joint mechanical effects produced by contraction of each hindlimb muscle and to predict muscle trajectories during a range of limb behaviors (wiping, defensive kicking, swimming and jumping). Through these analyses, we show that all hindlimb muscles have multiple functions with respect to accelerating the limb in its three-dimensional workspace and that the balance of functions depends greatly on limb configuration. In addition, we show that muscles have multiple, task-specific functions with respect to the type of contraction performed. The results of this study provide important data regarding the multifunctional role of hindlimb muscles in the frog and form a foundation upon which additional model subsystems (e.g. neural) and more sophisticated muscle models can be appended.

Animals↗