Adenosine 5'-triphosphate consumption by smooth muscle as predicted by the coupled four-state crossbridge model.
We have proposed a four-state crossbridge model to explain contraction and the latch state in arterial smooth muscle. Ca(2+)-dependent crossbridge phosphorylation was the only postulated regulatory mechanism and the latchbridge (a dephosphorylated, attached crossbridge) was the only novel element in the model. In this study, we used the model to predict rates of ATP consumption by crossbridge phosphorylation (JPhos) and cycling (JCycle) during isometric and isotonic contractions in arterial smooth muscle; then we compared model predictions with experimental data. The model predicted that JPhos and JCycle were similar in magnitude in isometric contractions, and both increased almost linearly with myosin phosphorylation. The predicted relationship between isometric stress and ATP consumption was quasihyperbolic, but approximately linear when myosin phosphorylation was below 35%, in agreement with most of the available data. Muscle shortening increased the predicted values of JCycle up to 3.7-fold depending on shortening velocity and the level of myosin phosphorylation. The predicted maximum work output per ATP was 7.4-7.8 kJ/mol ATP and was relatively insensitive to changes in myosin phosphorylation. The predicted increase in JCycle with shortening was in agreement with available data, but the model prediction that work output per ATP was insensitive to changes in myosin phosphorylation was unexpected and remains to be tested in future experiments.
Hai
C M
CM
Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912.
Murphy
R A
RA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D004734:Energy Metabolism; D007537:Isometric Contraction / Q000502:physiology; D007551:Isotonic Contraction / Q000502:physiology; D007700:Kinetics; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation
D000255:Adenosine Triphosphate; D009218:Myosins