Computational Mechanistic Investigation of Chronotropic Effects on Murine Sinus Node Cells

It has been shown for multiple species that the beating rate of the sinus node is sensitive to stretch. In rabbit an underlying stretch induced current has been experimentally established. Mathematical models implementing stretch as a non-selective stretch activated current were found to be consistent with the observed increased beating rate. In mice, a negative chronotropic response is observed experimentally. This leads to the question whether non-selective stretch activated currents can also cause a decreased beating rate. To investigate this, we used a mathematical model of murine sinus node cells and added an ohmic channel. Different levels of stretch were modelled by altering the conductance of the channel. As we increased stretch in the model, we found an initial decrease in beating rate followed by a monotonic increase, indicating that activation of stretch activated channels can cause opposite chronotropic effects in mice depending on stretch amplitude.