The biophysics of asthmatic airway smooth muscle.

Abstract

It is clear that significant advances have been made in the understanding of the physiology, biochemistry and molecular biology of airway smooth muscle (ASM) contraction and how the knowledge obtained from these approaches may be used to elucidate the pathogenesis of asthma. Not to belittle other theories of smooth muscle contraction extant in the field, perhaps the most outstanding development has been the formulation of plasticity theory. This may radically alter our understanding of smooth muscle contraction. Its message is that while shortening velocity and capacity are linear functions of length, active force is length independent. These changes are explained by the ability of thick filament protein to depolymerize at short lengths and to increase numbers of contractile units in series at lengths greater than optimal length or L(ref). Other advances are represented by the report that the major part of ASM shortening is complete within the initial first 20% of contraction time, that the nature and history of loading determine the extent of shortening and that these findings can be explained by the finding that the crossbridges are cycling four times faster than in the remaining time. Another unexpected finding is that late in the course of isotonic relaxation the muscle undergoes spontaneous activation which delays relaxation and smoothes it out; speculatively this could minimize turbulence of airflow. On the applied front evidence now shows the shortening ability of bronchial smooth muscle of human subjects of asthma is significantly increased. Measurements also indicate that increased smooth muscle myosin light chain kinase content, via increased actomyosin ATPase activity could be responsible for the changes in contractility.