Force maintenance and myosin filament assembly regulated by Rho-kinase in airway smooth muscle.

Smooth muscle contraction can be divided into two phases: the initial contraction determines the amount of developed force and the second phase determines how well the force is maintained. The initial phase is primarily due to activation of actomyosin interaction and is relatively well understood, whereas the second phase remains poorly understood. Force maintenance in the sustained phase can be disrupted by strains applied to the muscle; the strain causes actomyosin cross-bridges to detach and also the cytoskeletal structure to disassemble in a process known as fluidization, for which the underlying mechanism is largely unknown.

Ultrastructure of human tracheal smooth muscle from subjects with asthma and nonasthmatic subjects. Standardized methods for comparison.

A characteristic feature of asthma is exaggerated airway narrowing, termed airway hyper-responsiveness (AHR) due to contraction of airway smooth muscle (ASM). Although smooth muscle (SM)-specific asthma susceptibility genes have been identified, it is not known whether asthmatic ASM is phenotypically different from nonasthmatic ASM in terms of subcellular structure or mechanical function. The present study is the first to systematically quantify, using electron microscopy, the ultrastructure of tracheal SM from subjects with asthma and nonasthmatic subjects.

Airway contractility and remodeling: links to asthma symptoms.

Respiratory symptoms are largely caused by obstruction of the airways. In asthma, airway narrowing mediated by airway smooth muscle (ASM) contraction contributes significantly to obstruction. The spasmogens produced following exposure to environmental triggers, such as viruses or allergens, are initially responsible for ASM activation.

Regulatable stiffness in relaxed airway smooth muscle: a target for asthma treatment?

The airway smooth muscle (ASM) layer within the airway wall modulates airway diameter and distensibility. Even in the relaxed state, the ASM layer possesses finite stiffness and limits the extent of airway distension by the radial force generated by parenchymal tethers and transmural pressure. Airway stiffness has often been attributed to passive elements, such as the extracellular matrix in the lamina reticularis, adventitia, and the smooth muscle layer that cannot be rapidly modulated by drug intervention such as ASM relaxation by β-agonists.

Time course of isotonic shortening and the underlying contraction mechanism in airway smooth muscle.

Although the structure of the contractile unit in smooth muscle is poorly understood, some of the mechanical properties of the muscle suggest that a sliding-filament mechanism, similar to that in striated muscle, is also operative in smooth muscle. To test the applicability of this mechanism to smooth muscle function, we have constructed a mathematical model based on a hypothetical structure of the smooth muscle contractile unit: a side-polar myosin filament sandwiched by actin filaments, each attached to the equivalent of a Z disk. Model prediction of isotonic shortening as a function of time was compared with data from experiments using ovine tracheal smooth muscle.

Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis.

In this study, we compared the potencies of diosgenin, a plant-derived sapogenin structurally similar to estrogen and progesterone, on vascular smooth muscle functions ranging from contraction and migration to apoptosis. The effects of diosgenin on vascular smooth muscle cell viability and migration were measured using a primary mouse aortic smooth muscle cell culture. The effects of diosgenin on smooth muscle cell contraction and calcium signaling were investigated in the isolated mouse aorta using wire myography and confocal microscopy, respectively.

A comparative study of alpha-adrenergic receptor mediated Ca(2+) signals and contraction in intact human and mouse vascular smooth muscle.

In many vascular smooth muscle cells, physiological and pharmacological agonists initiate oscillatory fluctuations in intracellular Ca(2+) to initiate and maintain vasoconstriction. These oscillations are supported by the underlying cellular ultrastructure, particularly the close apposition between the plasma membrane (PM) and superficial sarcoplasmic reticulum (SR), the so-called PM-SR junctions, which are important for SR Ca(2+) refilling. We hypothesize that the disappearance of PM-SR junctions during aging and/or disease is directly related to the disappearance of agonist-induced Ca(2+) oscillations.

Adaptive response of pulmonary arterial smooth muscle to length change.

Hypervasoconstriction is associated with pulmonary hypertension and dysfunction of the pulmonary arterial smooth muscle (PASM) is implicated. However, relatively little is known about the mechanical properties of PASM. Recent advances in our understanding of plastic adaptation in smooth muscle may shed light on the disease mechanism.

ATP promotes NCX-reversal in aortic smooth muscle cells by DAG-activated Na+ entry.

Reversal of the plasma membrane Na(+)/Ca(2+) exchanger (NCX) has been shown to mediate Ca(2+) influx in response to activation of G-protein linked receptors. Functional coupling of reverse-mode NCX with canonical transient receptor potential channels (TRPC), specifically TRPC6, has recently been demonstrated by our laboratory to mediate Ca(2+) influx in rat aortic smooth muscle cells (RASMCs) following ATP stimulation. In this communication, we provide further detail of this functional coupling by indirectly measuring NCX reversal.

Possible mechanism of the vasodepressor effect of endokinin a/b in anesthetized rats.

We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.

Effect of neurokinins on canine prostate cell physiology.

Background: Sensory peptide neurotransmitters have been implicated as significant regulators of prostate growth. This study was designed to evaluate the role of neurokinins in proliferation, differentiation, and contraction of canine prostate cells in culture.

Methods: NK1, NK2, and NK3 receptor subtypes were localized in canine prostate tissue by immunocytochemistry and ligand binding studies.

Analysis of the mechanism of the vasodepressor effect of urocortin in anesthetized rats.

The aim was to examine if the depressor effect of urocortin involves activation of the nitric oxide (NO)/L-arginine pathway, production of prostanoids or opening of K(+)-channels. I. v.