The mechanical properties of triton-permeabilized ventricular preparations isolated from 4, 18 and 24-month-old F344 rats were analyzed to provide information about the molecular mechanisms that lead to age-related increases in diastolic myocardial stiffness in these animals. Passive stiffness (measured in solutions with minimal free Ca2+) did not change with age. This implies that the aging-associated dysfunction is not due to changes in titin or collagen molecules. Ca2+-activated preparations exhibited a characteristic short-range force response: force rose rapidly until the muscle reached its elastic limit and less rapidly thereafter. The elastic limit increased from 0.43 ± 0.01% l0 (where l0 is the initial muscle length) in preparations from 4-month-old animals to 0.49 ± 0.01% l0 in preparations from 24-month-old rats (p < 0.001, ANOVA). Relative short-range force was defined as the maximum force produced during the short-range response normalized to the prevailing tension. This parameter increased from 0.110 ± 0.002 to 0.142 ± 0.002 over the same age-span (p < 0.001, ANOVA). Analytical gel electrophoresis showed that the maximum stiffness of the preparations during the short-range response and the relative short-range force increased (p = 0.031 and p = 0.005 respectively) with the relative content of slow β myosin heavy chain molecules. Elastic limit values did not correlate with myosin isoform content. Simulations based on these results suggest that attached β myosin heavy chain cross-bridges are stiffer than links formed by α myosin heads. In conclusion, elevated content of stiffer β myosin heavy chain molecules may contribute to aging-associated increases in myocardial stiffness.
|Number of pages||8|
|Journal||Journal of Molecular and Cellular Cardiology|
|State||Published - Jan 2009|
Bibliographical noteFunding Information:
This work was supported by the American Heart Association Scientist Development Grant 0630079N, NIH AG021862, NIH HL 090749 (all to KSC) and the University of Kentucky Research Challenge Trust Fund.
- Contractile proteins
- Detergent skinned muscle
- Diastolic dysfunction
- Mathematical modeling
- Ventricular function
- Ventricular stiffness
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine