I organized this book because there is a need to put together in book form recent advances in our knowledge of how airway smooth muscle:works in health and in disease. After a period when it seemed that progress was very slow, there has been in the past few years an incredibly rapid gathering of knowledge in this area. In particular, our understanding has improved regarding the cascades of events that follow the initial binding of agonist to plasma membrane receptors and that lead to the cross-bridge movements that determine contraction. This advance in our knowledge was stimulated by use of single-and whole-cell channel recordings of plasma membrane currents and by description of the l3-receptor-GTP-binding protein-adenylate cyclase-cAMP coupling system, which serves as a model for other coupling mechanisms. The discovery of the receptor-activated inositol phospholipid transduction system has greatly stimulated research and led to advances in our understanding of mechanisms involved in smooth muscle con traction. Major advances were also triggered by the development of indicators for measuring free cytosolic calcium concentration and starting the unraveling of 2 the events involved in Ca + -dependent activation of contractile proteins. Al though most of the studies that led to our current understanding of these areas were performed on nonairway smooth muscle, these studies usually add to our understanding of airway smooth muscle, and there is an enlarging body of data that have been obtained on airway smooth muscle.

In this book, leading researchers in medicine and molecular pharmacology explain the cellular mechanisms that control airway smooth muscle. The means by which these are disrupted in disease, and the pharmacologic strategies by which they may be modified are discussed and future therapeutic interventions are identified. Aimed at specialists in pulmonology, this volume provides the clinician with the most up to date information on one of the core physiological processes in airway disease, and offers insights into current and future approaches to management. Authoritative update on key mechanisms of airway constriction in Asthma and COPD Relates latest research to bronchodilator therapy Multi-contributed text, co-coordinated by two of the leading authorities in the field.

This thesis focuses on the structure and function of airway smooth muscle (ASM) in health and disease. By employing the use of structural analysis by electron microscopy, functional analysis by mechanical measurements, and biochemical analysis, this thesis provides valuable insight into ASM pathophysiology. The first two chapters focus on the mechanisms by which the contractile apparatus is arranged within the cell. The studies examined whether the actin filament lattice acts a scaffold to facilitate myosin filament assembly within contractile units and the contractile response to potassium chloride (KCl). The muscle was treated with cytochalasin D (CD), a known actin filament disrupter, but this provided little insight on whether the actin lattice guides myosin filament assembly, since CD had a limited effect on actin filaments but a significant effect on force. KCl was found to cause contraction of similar force to acetylcholine contraction, despite the presence of fewer myosin filaments. KCl likely caused depolymerization of myosin filaments upon activation and allowed for force generation by non-filamentous myosin molecules. In the last two studies, human ASM was sourced from the tracheas of whole lungs donated for medical research. From this tissue source it was shown that, unlike in previous human ASM studies, human muscle is similar to that of other mammalian species and capable of significant isotonic shortening. This finding lends support to the use of animal ASM models as a proxy for human ASM. This also was the first study to examine human ASM in the paradigm of mechanical plasticity, using in situ muscle length as a reference length instead of the traditional Lmax, and was the first to demonstrate length adaptation in human ASM. The mechanical properties of asthmatic ASM were found to differ from those of non-asthmatic ASM at several key measurements. Asthmatic ASM was found to have an altered length-tension relationship, increased passive tension, and m.

This book presents the commonality and heterogeneity of the mechanisms underlying smooth muscle spontaneous activity in various smooth muscle organs and in addition discusses their malfunctions in disease and their potential as novel therapeutic targets. To facilitate understanding, the volume is divided into five parts and covers 16 organs: airways, gastrointestinal tract (phasic muscle, tonic muscle), renal pelvis, ureter, urinary bladder, urethra, corporal tissue, prostate, uterus, oviducts, seminal vesicle, artery, vein, microvasculature, and lymphatic vessels. This structure will help readers to comprehend the most up-to-date information on the similarities and differences in the contractile mechanisms driving various smooth muscles as well as their potential manipulations in particular visceral organ pathologies. The vast advancements in gene, electrical recording, and imaging technologies in this field are also discussed, with review of past achievements and consideration of likely future developments. This book will be of worldwide interest to clinicians, students, and researchers alike.

Airway smooth muscle plays a dominant role in bronchial asthma, as well as a significant role in various pulmonary diseases, such as chronic bronchitis, cystic fibrosis and emphysema. Myogenic, neurogenic, and humoral factors control airway smooth-muscle tone. This text provides a state-of-the-art summary and critical discussion of airway smooth muscle from a multidisciplinary point of view. Topics discussed include morphology, biochemical regulation, mechanical and electrophysiological behavior and reflex control of smooth muscle; the epithelium-derived relaxing factor; and methods to measure smooth muscle function in vivo in humans and experimental animals, as well as in vitro in isolated airway tissues. Also discussed are calcium and potassium channels and receptors for adrenergic, cholinergic and histaminergic systems in modulating receptor-response coupling in airway smooth muscle. Airway Smooth Muscle: Modulation of Receptors and Response provides essential information for researchers, teachers, pulmonary specialists and allergists, and students interested in learning about airway smooth muscle.

Most studies on autonomic innervation of smooth muscle have focused on the short-term mechanisms involved in neurotransmission in physiological and pathophysiological conditions. However recent obser vations of the long-term plasticity of this system, i. e. its capacity for regeneration and for compensatory change in pattern of innervation and expression of cotransmitters and receptors in ageing, following surgery, trauma or in disease, have indicated that an understanding of the mechanisms involved could influence the design of therapeutic regimes. There is increasing evidence for long-term communication between nerves and smooth muscle cells during development and throughout adult life. To date, the trophic interactions between nerves and airway musculature have attracted little interest, consequently, much of the information presented here is drawn from studies using other smooth muscles. However, the questions posed about trophic interactions dur ing development apply as much to airways smooth muscle neuroeffector systems as to other autonomic neuroeffector systems. These are: i) How do developing nerve fibres know where to go and how do they reach their target sites? ii) What determines the density and pattern of inner vation at reaching the effector? iii) How do the nerves survive and maintain their position once established? iv) What factors influence neurochemical differentiation such that genetically multipotential neu rones are triggered to synthesize one or combinations of neurotransmit ters? v) What influence do nerves have on the structure, function and receptor expression of their effector cells? vi) How do diseases interrupt these processes? - see [1].