Regulation Of Smooth Muscle Contraction

Sixth Annual Graduate Hospital Research Symposium REGULATION OF SMOOTH MUSCLE PROGRESS IN SOLVING THE PUZZLE Every so often a scientific conference comes at a time when everyone has new and exciting information, when old "dogmas" do not seem to be as well established, and when speakers and participants alike are ready to challenge interpretations of old and new experimental data. This was such a conference. What turns on a smooth muscle cell? The precise answer to this question has eluded scientists for much longer than I have been involved in the field. We know that an increase in cytosolic calcium is necessary and we know that phosphorylation of the 20 kDa myosin light chain is an important step in the process. We do not know if other processes are necessary for the initiation and lor maintenance of a smooth muscle contraction nor do we know if other processes modulate the regulation of contraction. The goal of the symposium on which this volume is based was to explore the most current hypotheses for the answers to these questions. I believe that after reading the chapters included in this volume, you will agree that this goal was achieved. The importance of calcium and calmodulin dependent myosin light chain phosphoryla tion in the regulation of smooth muscle contraction was reinforced by many presentations. However, the status of myosin light chain phosphorylation as a simple calcium dependent switch came under serious suspicion.

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.

Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.

This valuable resource provides a systematic account of the biochemistry of smooth muscle contraction. As a comprehensive guide to this rapidly growing area of research, it covers the structure and characteristic properties of contractile and regulatory proteins, with special emphasis on their predicted function in the live muscle. Also included in this book are intermediate filament proteins, and desmin and vimentin, whose function in smooth muscle is unknown; and several enzymes involved in the phosphorylation-dephosphorylation of contractile and other proteins.