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1 Biophysics, Radboud University, Nijmegen, Gld, Netherlands
2 Cell biology, Radboud University, Nijmegen, Gld, Netherlands
3 Physiology, LUMC, Leiden, Netherlands
4 Cell Biology, University of Nijmegen, Nijmegen, Netherlands
5 Dept. of Biophysics, Univ Nijmegen, Nijmegen, Netherlands
* To whom correspondence should be addressed. E-mail: s.gielen{at}science.ru.nl.
We have investigated synchronization and propagation of calcium oscillations, mediated by gap junctional excitation transmission. For that purpose we used an experimentally based model of normal rat kidney (NRK) cells, electrically coupled in a 1-dimensional configuration (linear strand). Fibroblasts such as NRK cells, can form an excitable syncytium and generate spontaneous inositol 1,4,5-triphosphate (IP3) mediated intracellular calcium waves, which may spread over a monolayer culture in a coordinated fashion. An intracellular calcium oscillation in a pacemaker cell causes a membrane depolarization from within that cell via Cl(Ca)-channels leading to a L-type Ca-channel based action potential in that cell. This action potential is then transmitted to the electrically connected neighbor cell and the calcium inflow during that transmitted action potential triggers a calcium wave in that neighbor cell by opening of IP3-receptor channels, causing calcium induced calcium release (CICR). In this way the calcium wave of the pacemaker cell is rapidly propagated by the electrically transmitted action potential. Propagation of action potentials in a strand of cells depends on the number of terminal pacemaker cells, on the GCaL conductance of the cells, and on the electric coupling between the cells. Our results show that the coupling between IP3-mediated calcium oscillations and action potential firing provides a robust mechanism for fast propagation of activity across a network of cells, which is representative for many other cell types such as gastrointestinal cells, urethral cells and pacemaker cells in the heart.
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