All three of the selected articles in this issue of theJournal of Applied Physiology relate to the plasticity of smooth muscle. This is an area that has recently gained considerable attention at several scientific meetings. It is an important area of investigation, especially as plasticity and smooth muscle function may underlie several pathophysiological conditions (e.g., asthma). The first Highlighted Topics article featured in this issue, “Effect of chronic passive length change on airway smooth muscle length-tension relationship,” by Wang et al. (p. 734–740), demonstrates the amazing ability of airway smooth muscle to adapt to changes in muscle length. The length-tension relationship is conventionally regarded as a functional manifestation of muscle structure that allows a change in the degree of overlap between thick and thin filaments and hence the ability of the muscle to generate force. The large shift in the length-tension relationship in muscle strips accommodated at different lengths shown in this study indicates that the structure of the filament lattice in smooth muscle is not permanent, and this is the axiom for the plasticity theory. Although the mechanism underlying the plastic behavior of smooth muscle is still being debated, the authors propose that the number of contractile units in series is dependent on the adapted muscle length. This implies that, during the adaptation period, contractile units could be added or subtracted from the serial array that spans the cell length. Such a mechanism has been shown to be operative in skeletal muscle during chronic adaptation to length changes although the time course of the changes is generally longer than is reported for smooth muscle in the present study. An interesting finding of this study is that the process of adaptation is accelerated if the muscle is activated periodically; nonetheless, adaptation occurs in relaxed muscles subjected to chronic length change, over a much longer time frame (e.g., hours vs. minutes). One can speculate that, whatever the mechanism responsible for the plastic reorganization of the contractile apparatus, the subcellular change is activation dependent; perhaps phosphorylation of certain proteins is required. A chronic shift in the length-tension relationship of airway smooth muscle could result from persistent airway narrowing due to tonic smooth muscle contraction or passive shortening of the muscle secondary to low lung volumes or decreased coupling of lung parenchymal recoil to the airway. Such a shift in the length-tension relationship would allow airway smooth muscle to generate maximal force even at a shortened length. In addition, this study demonstrated that the passive length-tension relationship is also shifted during adaptation. Thus, even in the absence of muscle activation, it would be more difficult to reverse airway narrowing by airway distension, as occurs with deep inspirations. Therefore, the fact that airway smooth muscle is capable of shifting its length-tension relationship may have profound implications with regard to airflow resistance.
The second Highlighted Topics article in this issue of the Journal, “Plasticity of airway smooth muscle stiffness and extensibility: role of length-adaptive mechanisms,” by Gunst and Wu (p. 741–749), provides evidence that the structure of tracheal smooth muscle cells may be acutely modulated in response to contraction under different mechanical conditions. A number of studies have shown that tracheal smooth muscle exhibits length-adaptive properties that enable it to optimize its contractility to the mechanical conditions under which it is activated. Length adaptation has been proposed to result from a plasticity of the cytoskeletal organization that enables the cell to acutely adapt its structure to changes in cell shape at different muscle lengths. Such changes in filament organization would be predicted to alter muscle stiffness and extensibility. In this study, muscle stiffness was evaluated by imposing high-frequency, small-amplitude length oscillations on the muscle that were too small to disrupt cross-bridge attachments. The extensibility of the muscles was assessed by measuring changes in length during imposed stretches over a given force range. The results demonstrate that tracheal smooth muscle tissues are significantly stiffer and less extensible after activation at a short muscle length than after activation at a long length, as would be expected if the array of cytoskeletal filaments was shorter and thicker after contraction at a short muscle length. Furthermore, this study shows that stiffness of the activated muscles can be decreased by stretching them beyond the length at which they were maintained during contractile activation and that this reduction in stiffness persists during subsequent maneuvers during the same activation period, suggesting a stretch-induced structural rearrangement. These properties are not accounted for by traditional sliding filament mechanisms for muscle contraction. The observations are consistent with the hypothesis that the contraction of airway smooth muscle at different lengths results in a remodeling of the contractile filament organization that persists for the duration of the activation period, unless mechanically disrupted by stretch. The structural plasticity of airway smooth muscle may provide a framework for interpreting the effects of lung volume maneuvers on airway responsiveness in vivo. This property could result in a decrease in airway distensibility and an increase in airway responsiveness with bronchoconstriction at low lung volumes, and it could explain the reduction in airway tone and responsiveness induced by a deep inspiration.
The final Highlighted Topics article in this issue, “Effect of the aldehyde acrolein on acetylcholine-induced membrane current in airway smooth muscle cells,” by Hyvelin et al. (p. 750–754), examines the effect of an environmental pollutant, acrolein, on the electrophysiological properties of airway smooth muscle cells. Previous studies have shown that ex vivo exposure of airways to environmental pollutants alters airway smooth muscle responsiveness, suggesting that this effect may partially account for pollutant-induced in vivo bronchial hyperresponsiveness. In vitro experimental models facilitate the analysis of cellular and molecular mechanisms implicated in the health effects of air pollution. With the use of the patch-clamp technique applied to freshly isolated airway smooth muscle cells, ACh and caffeine have been observed to activate a concentration-dependent inward Ca2+-activated Cl− current [I Cl(Ca)]. In agreement with recent findings on Ca2+ signaling in airway smooth muscle cells, the investigators also show that ACh inducesI Cl(Ca) oscillations, whereas caffeine induces only a single transient membrane current. The major finding of this study is that exposure to acrolein enhances both the amplitude of the ACh-induced I Cl(Ca) (at low ACh concentrations) and the frequency of the ACh-induced I Cl(Ca)oscillations (at high ACh concentrations). In contrast, acrolein did not alter the caffeine-induced transient I Cl(Ca)response. The influence of acrolein on the ACh-inducedI Cl(Ca) response results from its effect on Ca2+ signaling. At the cellular level, ACh-induced cytosolic Ca2+ oscillations in airway smooth muscle cells are concentration dependent, involving cyclic Ca2+ release from and reuptake into intracellular Ca2+ stores, with release primarily mediated by inositol trisphosphate mechanisms. Therefore, an effect of acrolein on intracellular Ca2+ is likely responsible for the acrolein-induced effects on airway smooth muscle mechanical activity. Furthermore, acrolein-induced increases inI Cl(Ca) may, in turn, promote membrane depolarization, which would also contribute to an increase in mechanical tone. This study clearly demonstrates plasticity of airway smooth muscle under pathophysiological conditions reflected by exposure to air pollutants.
- Copyright © 2001 the American Physiological Society