Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma
Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2000.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2005
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/9372 |
| _version_ | 1826189147909390336 |
|---|---|
| author | Inouye, David Shoichi |
| author2 | Jeffrey J. Fredberg. |
| author_facet | Jeffrey J. Fredberg. Inouye, David Shoichi |
| author_sort | Inouye, David Shoichi |
| collection | MIT |
| description | Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2000. |
| first_indexed | 2024-09-23T08:10:16Z |
| format | Thesis |
| id | mit-1721.1/9372 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T08:10:16Z |
| publishDate | 2005 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/93722022-01-13T07:53:45Z Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma Inouye, David Shoichi Jeffrey J. Fredberg. Harvard University--MIT Division of Health Sciences and Technology. Harvard University--MIT Division of Health Sciences and Technology Harvard University--MIT Division of Health Sciences and Technology. Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2000. "September 1999." Includes bibliographical references (leaves 139-145). In asthma, the key effector driving acute airway narrowing is thought to be airway smooth muscle (ASM); as the muscle surrounding the airways shortens, the airway lumen narrows. Airway hyperresponsiveness (AHR) - the excessive narrowing of the airways - is one of the cardinal features of asthma. Yet, the mechanism(s) regulating the airway lumenal radius, and perhaps the failure of these mechanisms to prevent excessive airway constriction, remains largely unexplained. This thesis shows that the regulation of ASM length corresponds to a dynamically equilibrated steady-state, not the static mechanical equilibrium that had been previously assumed. This dynamic steady state requires as an essential feature a continuous supply of external mechanical energy (derived from tidal lung inflations) that act to perturb the interactions of myosin with actin, drive the molecular state of the system far away from thermodynamic equilibrium, and bias the muscle toward lengthening. This mechanism leads naturally to the suggestion that excessive airway narrowing in asthma may be associated with the destabilization of that dynamic process and its resulting collapse back to static equilibrium. With this collapse the muscle undergoes a phase transition and virtually freezes at its static equilibrium length. This mechanism may help to elucidate several unexplained phenomena including the multi-factorial origins of AHR, how allergen sensitization leads to AHR, and the inability in asthma of deep inspiration to relax ASM. by David Shoichi Inouye. Ph.D. 2005-08-22T20:40:58Z 2005-08-22T20:40:58Z 2000 Thesis http://hdl.handle.net/1721.1/9372 44804247 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 156 p. 10262982 bytes 10262739 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Harvard University--MIT Division of Health Sciences and Technology. Inouye, David Shoichi Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| title | Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| title_full | Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| title_fullStr | Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| title_full_unstemmed | Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| title_short | Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| title_sort | perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma |
| topic | Harvard University--MIT Division of Health Sciences and Technology. |
| url | http://hdl.handle.net/1721.1/9372 |
| work_keys_str_mv | AT inouyedavidshoichi perturbedequilibriaofmyosinbindinginairwaysmoothmuscleanditsimplicationsinairwayhyperresponsivenessandasthma |