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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 oflikely future developments. This book will be of worldwide interest to clinicians, students, and researchers alike.

This book explores the role calcium signaling plays in cellular responses in almost all types of cells including airway smooth muscle cells. This universal signaling may result from extracellular calcium influx and/or intracellular calcium release, which are precisely controlled and regulated by ion channels, exchangers and/or transporters on the plasmalemmal or sarcoplasmic reticulum membrane. First, several chapters detail calcium release channels (ryanodine receptors and inositol trisphosphate receptors), voltage-dependent potassium channels, transient receptor potential channels, Orai channels, calcium-activated potassium channels, and calcium-activated chloride channels. Well-characterized sodium-calcium exchangers, voltage-dependent calcium channels, and calcium pumps are described also in depth over many chapters. Ca2+ signaling can be expressed in Ca2+ sparks, waves, oscillations, and global changes in intracellular Ca2+ concentration. Calcium in subcellular compartments (cytosol, sarcoplasmic reticulum, mitochondria, and caveolae) also exhibit dynamic crosstalk. Many molecules including FK506 binding proteins, cyclic adenosine diphosphate ribose, reactive oxygen species, RhoA kinases, caveolin and integrins can modify and induce spatial, temporal and compartmental variations of calcium signaling. In addition, calcium signaling can exhibit sex hormone- and age-dependent changes. A number of chapters are dedicated to covering these diverse formats, spatiotemporal characteristics, multifaceted network and mathematical modeling of Ca2+ signaling. Neurotransmitters, hormones, growth factors, inflammatory cytokines, and other stimuli may lead to multiple cellular responses by inducing Ca2+ signaling in airway smooth muscle cells. Increasing evidence suggests that Ca2+ pumps and canonical transient receptor potential channels are essential for airway smooth muscle remodeling. Accordingly, several chapters summarize recent advances in the studies of the key role of calcium signaling in physiological cellular responses as well as the development of asthma, chronic obstructive pulmonary disease and other respiratory disorders.

Many factors may influence the release of neurotransmitters from airway nerves [1]. This is likely to be important in physiological control of airway functions and may be particularly relevant in airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Neural elements in airways interact in a complex manner and the activation of certain neural pathways may profoundly influence the release of transmitters from other neural pathways. Similarly inflamma­ tory mediators released from inflammatory cells in the airways may also modulate neurotransmitter release. There are marked differences be­ tween species in airway innervation and in neuromodulatory effects and, wherever possible, studies in human airways have been emphasised, although information on neuromodulation in human airways is some­ what limited at present. Release of neurotransmitters from nerve terminals occurs via a Ca2+­ dependent secretion evoked by a nerve action potential, but may also be evoked experimentally by a high extracellular K + concentration which directly depolarises the nerve terminal membrane. Modulation refers to the alteration of neurotransmitter release, which may either be increased (facilitation) or reduced (inhibition) by the action of a particular agent, thus changing the magnitude of the neurally-mediated response. Such agents would normally act on receptors on the nerve terminal which are referred to as pre-junctional (or presynaptic) receptors, in contrast to post-junctional (or post-synaptic) receptors located on the target cells which are influenced by that particular transmitter.