Uterine smooth muscle cells (USMCs) undergo ionic channel remodelling during gestation to facilitate spontaneous action potential (AP)-driven contractions during labour. Electrical activity of USMCs is related to the intracellular Ca2+ dynamics which in turn controls their contraction. Simple models of [Ca2+]i dynamics and mechanics of USMCs are available but a rigorous model for the membrane excitation is lacking. The aim of this study was to construct a mathematical description of an USMC at the late pregnant stage with biophysically detailed membrane electrophysiology. Mathematical models for thirteen ionic currents were developed based on voltage-clamp experimental data of late pregnant rat and human tissues in the literature. Several inward currents were considered: L-type Ca2+ current, attributed to be the major inward current, fast Na+ current, T-type Ca2+ current and an hyperpolarisation-activated current. The outward currents include: fast A-type transient K+ current, two voltage-gated K+ currents (IK1 and IK2), Ca2+-activated K+ current and a sustained background current. Ca2+-activated Cl– current and a non-specific cation current, each have reversal potentials within the reported AP amplitude range, are also included. All currents are modelled as ohmic resistors and their conductance kinetics described by Hodgkin-Huxley-type first order ordinary differential equations. Currents of a Na+-Ca2+ exchanger and a Na+-K+ pump are also included to allow incorporation of [Ca2+]i dynamics (via the membrane channels, the Na+-Ca2+ exchanger and the plasma membrane Ca2+-ATPase) modified from a simple uterine excitation-contraction model [1]. The model was initially validated by the ability to produce bursting APs by an external stimulus. In Figure 1(a), repetitive APs were evoked by a current clamp consistent with experimental recordings from myometrium of pregnant rats [2]. Further model parameterisation was evidenced by the ability to closely simulate the effects of oestradiol, which modulates the amplitude and activation properties of individual Ca2+ and K+ currents, to alter AP configuration to a tonic-like plateau [2-4]. In conclusion, a novel mathematical model of the electrical action potential of USMCs has been developed. This provides a powerful tool to investigate the ionic mechanisms underlying the physiological genesis of electrical excitation governing labouring contractions.
University of Cambridge (2008) Proc Physiol Soc 11, PC145
Poster Communications: Mathematical modelling of electrical action potentials in a uterine smooth muscle cell
W. Tong1, C. Y. Choi1, H. Zhang1, M. J. Taggart2
1. School of Physics and Astronomy, University of Manchester, Manchester, United Kingdom. 2. Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom.
View other abstracts by:
Figure 1. Simulated membrane action potential (V) of a USMC of pregnant rat in the absence (a) or presence (b) of oestradiol [2]. Current clamp applied at time = 1 - 3 s.
Where applicable, experiments conform with Society ethical requirements.