Key result
In a computational model of murine sinus node cells, increasing stretch caused an initial decrease in beating rate followed by a monotonic increase, demonstrating amplitude-dependent opposite chronotropic effects.
Why the study?
Mice experimentally display a negative chronotropic response to stretch, raising the question of whether non-selective stretch-activated currents can also cause a decreased beating rate.
Computational modeling and experimental data demonstrate that stretch-activated channels can cause a negative chronotropic response in murine sinus node cells, contrasting with the positive response seen in rabbits.
Answers are grounded in this paper and cite their sources.
Species differences in stretch-induced sinus node responses warrant caution extrapolating to humans; challenges uniform positive chronotropy and leaves mechanisms open.
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.
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Winkelmann et al. (2018) studied Sinus node stretch response (n=1). Stretch (experimental and computational modeling) vs. No stretch (0 mm or 0 pS/pF) was evaluated on Beating rate (BR) / Action potential frequency. In a computational model of murine sinus node cells, increasing stretch caused an initial decrease in beating rate followed by a monotonic increase, demonstrating amplitude-dependent opposite chronotropic effects.
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