title: Myosin head orientation: a structural determinant for the Frank-Starling relationship.
abstract: 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(1,1)/I(1,0) intensity ratio decreases, whereas the M3 meridional reflection intensity (I(M3)) increases, concomitant with increases in diastolic and systolic force. Using a short (∼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 I(M3)) 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.
authors: James R. DePauw Professor of Physiology, Dept. of Cell and Molecular Physiology, Loyola Univ. Chicago, 2160 South First Ave., Stritch School of Medicine, Maywood, IL, 60153-5500, USA.
authors: Gerrie P
authors: GP
authors: Farman
authors: David
authors: D
authors: Gore
authors: Edward
authors: E
authors: Allen
authors: Kelly
authors: K
authors: Schoenfelt
authors: Thomas C
authors: TC
authors: Irving
authors: Pieter P
authors: PP
authors: de Tombe
mesh_terms: D008841:Actin Cytoskeleton / Q000000981:diagnostic imaging* / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000737:chemistry* / Q000378:metabolism; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains; D012518:Sarcomeres / Q000000981:diagnostic imaging / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology*; D014961:X-Ray Diffraction
chemical_list: D018995:Myosin Heavy Chains; D009218:Myosins