Following a step increase in sarcomere length, isometric cardiac muscle ten
sion increases instantaneously by the Frank-Starling mechanism. Ln isolated
papillary muscle and myocytes, there is an additional significant rise in
developed tension over the following 15 min due to an unknown mechanism. Th
is slow change in tension could not be explained by mechanical heterogeneit
y of the muscle preparations or by an increase in myofilament sensitivity t
o Ca2+. The slow change in tension was not dependent on sarcoplasmic reticu
lum Ca2+ loading assessed with rapid cooling contractures, and was not sign
ificantly altered by sarcoplasmic reticulum Ca2+ depletion (ryanodine) or i
nhibition of sarcoplasmic reticulum Ca2+ reuptake (cyclopiazonic acid). We
used the Luo-Rudy ionic model of the ventricular myocyte together with a mo
del of the length-dependent myofilament activation by Ca2+ to examine the e
ffects of step changes in the parameters of sarcolemmal ion fluxes as possi
ble 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, sugg
esting that the slow change in stress may be caused by length induced chang
es 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 investiga
tion represents a valuable technique in elucidating the cellular mechanisms
of fundamental processes in cardiac excitation-contraction coupling.