Vladimir Matchkov

Introduction: Smooth muscle cells in the wall of endothelium denuded mesenteric arteries display uncoordinated calcium waves when exposed to nor-adrenaline. However, the cell population shows a considerable heterogeneity with some cells displaying waves of variable frequency whilst others remain quiet. At the onset of vasomotion however, all cells, including those that were previously quiet, are forced into synchronized oscillation. We hypothesize that this entrainment of previously quiet cells is caused by the driving force from a collective cyclic variation in membrane potential.

Methods: A combination of experiments and modeling was used. Wave frequency and the fraction of quiet cells were measured in separate experiments. In a mathematical model of coupled smooth muscle cells, morphologic heterogeneity was introduced by varying the volume fraction of the cells occupied by SR. The full spatially distributed model was then simulated.

Simulated results: A uniform increase in cytoplasmic [IP₃] increases the number of cells showing waves while a certain fraction of the cells remains quiet. An increase in [cGMP] shifts the oscillatory pattern from waves to global calcium oscillations and causes the onset of oscillations in membrane potential and intercellular synchronization. Previously quiet cells are forced into an oscillatory mode by the recurring collective variation in membrane potential which causes cyclic fluxes of calcium across the plasma membrane.

Conclusion: The combination of cellular heterogeneity and synchronized variation in membrane potential in coupled cells may provide a simple explanation for the observed entrainment of quiet cells at the onset of vasomotion.