a computational model of the ionic currents, ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle离子电流的计算模型,ca2 +动力学和潜在孤立的子宫平滑肌收缩动作电位.pdfVIP

A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle 1,2 3 3 4 3 Wing-Chiu Tong , Cecilia Y. Choi , Sanjay Karche , Arun V. Holden , Henggui Zhang *, Michael J. Taggart1,2* 1 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, 2 Maternal and Fetal Health Research Centre, St. Mary’s Hospital, University of Manchester, Manchester, United Kingdom, 3 School of Physics and Astronomy, University of Manchester, Manchester, United Kingdom, 4 Institute of Membrane and System Biology, University of Leeds, Leeds, United Kingdom Abstract Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2 z currents (L- and T-type), Na z current, an hyperpolarization-activated current, three voltage-gated Kz currents, two Ca2 z-activated Kz current, Ca2 z-activated Cl current, non-specific cation current, Na z-Ca2 z exchanger, Na z-Kz pump and bac