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Am J Physiol Cell Physiol 292: C1816-C1829, 2007. First published January 31, 2007; doi:10.1152/ajpcell.00478.2006
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Mathematical model of excitation-contraction in a uterine smooth muscle cell

Limor Bursztyn,1 Osnat Eytan,2 Ariel J. Jaffa,2,3 and David Elad1

1Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University; 2Ultrasound Unit in Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center; and 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Submitted 7 September 2006 ; accepted in final form 25 January 2007

Uterine contractility is generated by contractions of myometrial smooth muscle cells (SMCs) that compose most of the myometrial layer of the uterine wall. Calcium ion (Ca2+) entry into the cell can be initiated by depolarization of the cell membrane. The increase in the free Ca2+ concentration within the cell initiates a chain of reactions, which lead to formation of cross bridges between actin and myosin filaments, and thereby the cell contracts. During contraction the SMC shortens while it exerts forces on neighboring cells. A mathematical model of myometrial SMC contraction has been developed to study this process of excitation and contraction. The model can be used to describe the intracellular Ca2+ concentration and stress produced by the cell in response to depolarization of the cell membrane. The model accounts for the operation of three Ca2+ control mechanisms: voltage-operated Ca2+ channels, Ca2+ pumps, and Na+/Ca2+ exchangers. The processes of myosin light chain (MLC) phosphorylation and stress production are accounted for using the cross-bridge model of Hai and Murphy (Am J Physiol Cell Physiol 254: C99–C106, 1988) and are coupled to the Ca2+ concentration through the rate constant of myosin phosphorylation. Measurements of Ca2+, MLC phosphorylation, and force in contracting cells were used to set the model parameters and test its ability to predict the cell response to stimulation. The model has been used to reproduce results of voltage-clamp experiments performed in myometrial cells of pregnant rats as well as the results of simultaneous measurements of MLC phosphorylation and force production in human nonpregnant myometrial cells.

cellular calcium control mechanisms; myometrial contractions; myosin light chain phosphorylation



Address for reprint requests and other correspondence: L. Bursztyn, Dept. of Biomedical Engineering, Faculty of Engineering, Tel Aviv Univ., Tel Aviv 69978, Israel (e-mail: burszty{at}post.tau.ac.il and elad{at}eng.tau.ac.il)







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