Open Access. Powered by Scholars. Published by Universities.®
- Keyword
Articles 1 - 2 of 2
Full-Text Articles in Life Sciences
Recent Insights Into Muscle Fatigue At The Cross-Bridge Level, Edward Debold
Recent Insights Into Muscle Fatigue At The Cross-Bridge Level, Edward Debold
Edward P. Debold
The depression in force and/or velocity associated with muscular fatigue can be the result of a failure at any level, from the initial events in the motor cortex of the brain to the formation of an actomyosin cross-bridge in the muscle cell. Since all the force and motion generated by muscle ultimately derives from the cyclical interaction of actin and myosin, researchers have focused heavily on the impact of the accumulation of intracellular metabolites [e.g., Pi, H+ and adenosine diphoshphate (ADP)] on the function these contractile proteins. At saturating Ca++ levels, elevated Pi appears to be the primary cause for …
Cardiac Myosin Missense Mutations Cause Dilated Cardiomyopathy In Mouse Models And Depress Molecular Motor Function, Joachim Schmitt, Edward Debold, Ferhaan Ahmad, Amy Armstrong, Andrea Frederico, David Conner, Ulrike Mende, Martin Lohse, David Warshaw, Christine Seidman, J. Seidman
Cardiac Myosin Missense Mutations Cause Dilated Cardiomyopathy In Mouse Models And Depress Molecular Motor Function, Joachim Schmitt, Edward Debold, Ferhaan Ahmad, Amy Armstrong, Andrea Frederico, David Conner, Ulrike Mende, Martin Lohse, David Warshaw, Christine Seidman, J. Seidman
Edward P. Debold
Dilated cardiomyopathy (DCM) leads to heart failure, a leading cause of death in industrialized nations. Approximately 30% of DCM cases are genetic in origin, with some resulting from point mutations in cardiac myosin, the molecular motor of the heart. The effects of these mutations on myosin's molecular mechanics have not been determined. We have engineered two murine models characterizing the physiological, cellular, and molecular effects of DCM-causing missense mutations (S532P and F764L) in the α-cardiac myosin heavy chain and compared them with WT mice. Mutant mice developed morphological and functional characteristics of DCM consistent with the human phenotypes. Contractile function …