Myosin head orientation: a structural determinant for the Frank-Starling relationship
- IIT
The cellular mechanism underlying the Frank-Starling law of the heart is myofilament length-dependent activation. The mechanism(s) whereby sarcomeres detect changes in length and translate this into increased sensitivity to activating calcium has been elusive. Small-angle X-ray diffraction studies have revealed that the intact myofilament lattice undergoes numerous structural changes upon an increase in sarcomere length (SL): lattice spacing and the I{sub 1,1}/I{sub 1,0} intensity ratio decreases, whereas the M3 meridional reflection intensity (I{sub M3}) increases, concomitant with increases in diastolic and systolic force. Using a short ({approx}10 ms) X-ray exposure just before electrical stimulation, we were able to obtain detailed structural information regarding the effects of external osmotic compression (with mannitol) and obtain SL on thin intact electrically stimulated isolated rat right ventricular trabeculae. We show that over the same incremental increases in SL, the relative changes in systolic force track more closely to the relative changes in myosin head orientation (as reported by IM3) than to the relative changes in lattice spacing. We conclude that myosin head orientation before activation determines myocardial sarcomere activation levels and that this may be the dominant mechanism for length-dependent activation.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- OTHER
- OSTI ID:
- 1019126
- Journal Information:
- Am. J. Physiol.-Heart C, Journal Name: Am. J. Physiol.-Heart C Journal Issue: (6) ; 06, 2011 Vol. 300; ISSN 0363-6135
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Mechanisms of a novel regulatory light chain–dependent cardiac myosin inhibitor
Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure