Computational Modeling Reveals Key Contributions of KCNQ and XXXX Currents to the Malleability of Uterine Action Potentials Underpinning Labor.

@entity2045 @entity9493 @entity6763
The electrical excitability of uterine smooth muscle cells is a key determinant of the contraction of the organ during labor and is manifested by spontaneous, periodic @entity2045 ( @entity2045 ). Near the end of term, @entity2045 vary in shape and size reflecting an ability to change the frequency, duration and amplitude of uterine contractions. A recent mathematical model quantified several ionic features of the electrical excitability in uterine smooth muscle cells. It replicated many of the experimentally recorded uterine AP configurations but its limitations were evident when trying to simulate the long-duration bursting @entity2045 characteristic of labor. A computational parameter search suggested that delayed rectifying K+ currents could be a key model component requiring improvement to produce the longer-lasting bursting @entity2045 . Of the delayed rectifying K+ currents family it is of interest that KCNQ and @entity9493 channels have been reported to be gestationally regulated in the uterus. These currents exhibit features similar to the broadly defined uterine @entity6763 of the original mathematical model. We thus formulated new quantitative descriptions for several IKCNQ and IhERG. Incorporation of these currents into the uterine cell model enabled simulations of the long-lasting bursting @entity2045 . Moreover, we used this modified model to simulate the effects of different contributions of IKCNQ and IhERG on AP form. Our findings suggest that the alterations in expression of @entity9493 and KCNQ channels can potentially provide a mechanism for fine tuning of AP forms that lends a malleability for changing between plateau-like and long-lasting bursting-type @entity2045 as uterine cells prepare for parturition.
