Perturbed equilibrium of myosin binding in airway smooth muscle and its implications in bronchospasm

In asthma, the mechanisms relating airway obstruction, hyperresponsiveness, and inflammation remain rather mysterious. We show here that regulation of airway smooth muscle length corresponds to a dynamically equilibrated stea dy state, not the static mechanical equilibrium that had been previously as sumed. This dynamic steady state requires as an essential feature a continu ous supply of external mechanical energy (derived from tidal lung inflation s) that acts to perturb the interactions of myosin with actin, drive the mo lecular state of the system far away from thermodynamic equilibrium, and bi as the muscle toward lengthening. This mechanism leads naturally to the sug gestion that excessive airway narrowing in asthma may be associated with th e destabilization of that dynamic process and its resulting collapse back t o static equilibrium. With this collapse the muscle undergoes a phase trans ition and virtually freezes at its static equilibrium length. This mechanis m may help to elucidate several unexplained phenomena including the multifa ctorial origins of airway hyperresponsiveness, how allergen sensitization l eads to airway hyperresponsiveness, how hyperresponsiveness can persist lon g after airway inflammation is resolved, and the inability in asthma of dee p inspirations to relax airway smooth muscle.