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Lincoln E Ford

Publications and source records attributed to Lincoln E Ford.

8 recordsLinked to original sources
PubMed2006

Inhibition of myosin light-chain phosphorylation inverts the birefringence response of porcine airway smooth muscle.

Muscle birefringence, caused mainly by parallel thick filaments, increases in smooth muscle during stimulation, signalling thick filament formation upon activation. The reverse occurs in skeletal muscle, where a decrease in birefringence has been correlated with crossbridge movement away from the thick filaments. When force generation by trachealis muscle was inhibited with wortmannin, which inhibits myosin light-chain phosphorylation and thick-filament formation, but not the calcium increase caused by stimulation, the birefringence response inverted, suggesting crossbridge movement similar to that of skeletal muscle. Resistance to quick stretches was much greater in stimulated muscle than in unstimulated muscle before wortmannin treatment and no different in stimulated and unstimulated muscle after force inhibition by wortmannin. Before wortmannin treatment, stimulation reduced thick-filament cross-sectional areas in electron micrographs by 44%. After force inhibition by wortmannin, filament areas were not significantly different in stimulated and unstimulated muscle and not significantly different from those of relaxed muscle without wortmannin treatment. These results suggest that myofibrillar-space calcium causes crossbridges to move away from the thick filaments without firmly attaching to thin filaments.

Androstadienes↗
PubMed2005

Plasticity in airway smooth muscle: an update.

At a similar meeting 10 years ago, we proposed (i) that the long functional range of some smooth muscles is accommodated by plastic alterations that place more myofilaments in series at longer lengths, (ii) that this plasticity is facilitated by myosin filament evanescence, with filaments dissociating partially during relaxation and reforming upon activation, and (iii) that filament lengthening during the rise of activation would cause velocity to fall. Since that meeting, we have accumulated a substantial body of evidence to support these proposals, as follows: (i) muscles develop nearly the same force when adapted to a range of lengths that can vary by 3-fold; (ii) other physiological parameters including shortening velocity, maximum power, compliance, ATPase rate, and thick-filament mass increase by about 2/3 for a doubling of muscle length; (iii) thick-filament density increases substantially during the rise of activation; and (iv) velocity falls as force rises during the rise of tetanic force, and when correction is made for differences in activation, velocity and force vary exactly in inverse proportion. This review explains the rationale for the different experimental measurements and their interpretation.

Actin Cytoskeleton↗
PubMed2004

Length-dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle.

Birefringence and force produced by pig tracheal smooth muscles were recorded every 100 ms during electrically stimulated tetani at muscle lengths that varied 1.5-fold and at the peak of acetylcholine contractures at the same lengths. Isometric force was nearly the same at all lengths. Resting birefringence at the longest length was 30% greater than that at the shortest length. During tetani, birefringence increased with approximately the same time course as force, rising by 20% at the shortest length and 9% at the longest length, and continued to increase by an additional 0.5-1.5% of the resting value for 2-8 s after stimulation ended and force began to fall. This late increase was greatest and more sustained at longer lengths. During contractures, birefringence increased by 25 and 18% at the shortest and longest lengths, respectively. Comparison of these results with our published thick-filament densities suggests that thick-filament density increased by about 80, 72 and 50% during contractures at the short, intermediate and long lengths, and that approximately 35% of birefringence in the resting muscle at the longest length was not due to thick filaments. These findings support the hypotheses that tracheal smooth muscle adapts to longer lengths by increasing thick-filament mass and that myosin thick filaments are evanescent, dissociating partially during relaxation and reforming upon activation. The results further suggest that thick-filament formation is sufficiently rapid to account for the velocity slowing and some of the force increase observed during the rise of activation of tracheal smooth muscle.

Animals↗
PubMed2004

On the terminology for describing the length-force relationship and its changes in airway smooth muscle.

The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the length-force relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term "optimal length" (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of "length adaptation" to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously.

Animals↗
PubMed2003

Force and myosin light chain phosphorylation in dog airway smooth muscle activated in different ways.

To assess activation mechanisms of dog trachealis muscle and test whether isometric force generation could be separated from myosin light-chain (MLC) phosphorylation, force and phosphorylation were measured in the presence of wortmannin (a light-chain kinase inhibitor) or Y-27632 (a rho-kinase inhibitor) during electrically stimulated tetani and sustained contractures induced by acetylcholine, KCl, or calyculin A, a light-chain phosphatase inhibitor which caused irreversible contractures and both di- and mono-phosphorylation of light chain. Phosphorylation was not much more than half under any circumstances. A nearly constant proportionality between steady force and phosphorylation existed over a 9-fold force range during contractures and 25-sec tetani, except that force correlated best with the di-phosphorylated light chain produced by calyculin A. Phosphorylation was disproportionately higher than force at the outset of tetani, and this disproportion was exaggerated by Y-27632. The results suggest that about half the light chain is sequestered from kinases and that mechanical activation is tightly linked to phosphorylation, except at the outset of stimulation.

Acetylcholine↗
PubMed2003

Structure-function correlation in airway smooth muscle adapted to different lengths.

Airway smooth muscle is able to adapt and maintain a nearly constant maximal force generation over a large length range. This implies that a fixed filament lattice such as that found in striated muscle may not exist in this tissue and that plastic remodeling of its contractile and cytoskeletal filaments may be involved in the process of length adaptation that optimizes contractile filament overlap. Here, we show that isometric force produced by airway smooth muscle is independent of muscle length over a twofold length change; cell cross-sectional area was inversely proportional to cell length, implying that the cell volume was conserved at different lengths; shortening velocity and myosin filament density varied similarly to length change: increased by 69.4% +/- 5.7 (SE) and 76.0% +/- 9.8, respectively, for a 100% increase in cell length. Muscle power output, ATPase rate, and myosin filament density also have the same dependence on muscle cell length: increased by 35.4% +/- 6.7, 34.6% +/- 3.4, and 35.6% +/- 10.6, respectively, for a 50% increase in cell length. The data can be explained by a model in which additional contractile units containing myosin filaments are formed and placed in series with existing contractile units when the muscle is adapted at a longer length.

Adaptation, Physiological↗
PubMed2002

Differing effects of inotropic agents on length change deactivation of isolated rat myocardium.

BACKGROUND: A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced. METHODS: Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation. RESULTS: Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12+/-4% (mean+/-SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16+/-5%, decreased time to peak by 34+/-3%, and increased the deactivation slope by 106+/-9% (P<0.001). Caffeine had variable effects on peak force, increased time to peak by 47+/-4%, and decreased the deactivation slope by 71+/-5% (P<0.001). CONCLUSIONS: The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity.

Animals↗