title: Cellular mechanisms for the slow phase of the Frank-Starling response.
abstract: Following a step increase in sarcomere length, isometric cardiac muscle tension increases instantaneously by the Frank-Starling mechanism. In isolated papillary muscle and myocytes, there is an additional significant rise in developed tension over the following 15 min due to an unknown mechanism. This slow change in tension could not be explained by mechanical heterogeneity of the muscle preparations or by an increase in myofilament sensitivity to Ca2+. The slow change in tension was not dependent on sarcoplasmic reticulum Ca2+ loading assessed with rapid cooling contractures, and was not significantly altered by sarcoplasmic reticulum Ca2+ depletion (ryanodine) or inhibition of sarcoplasmic reticulum Ca2+ reuptake (cyclopiazonic acid). We used the Luo-Rudy ionic model of the ventricular myocyte together with a model of the length-dependent myofilament activation by Ca2+ to examine the effects of step changes in the parameters of sarcolemmal ion fluxes as possible mechanisms for the slow change in stress. The slow increase in tension was simulated by step changes in the Na+-K+ pump or Na+ leak currents, suggesting that the slow change in stress may be caused by length induced changes in Na+ fluxes. The model also predicted a slow increase in the magnitude of the initial repolarization during phase 1 of the action potential. The combination of experimental and computational models used in this investigation represents a valuable technique in elucidating the cellular mechanisms of fundamental processes in cardiac excitation-contraction coupling.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0412, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Bluhm
authors.forename: D
authors.initials: D
authors.lastname: Sung
authors.forename: W Y
authors.initials: WY
authors.lastname: Lew
authors.forename: A
authors.initials: A
authors.lastname: Garfinkel
authors.forename: A D
authors.initials: AD
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010210:Papillary Muscles / Q000166:cytology / Q000502:physiology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D016276:Ventricular Function