A theoretical study on the role of Ca(2+)-activated K+ channels in the regulation of hormone-induced Ca2+ oscillations and their synchronization in adjacent cells.

BACKGROUND INFORMATION

In many non-excitable cells hormone stimulation triggers repetitive oscillations of the intracellular Ca(2+) concentration, thought to be important in several cell functions. Although most of these cells respond to an elevation of the intracellular Ca(2+) concentration with a membrane hyperpolarization, due to the activation of Ca(2+)-activated K(+) channels, theoretical models do not usually consider the contribution of the membrane potential dynamics in defining the properties of the intracellular Ca(2+) concentration oscillations and their synchronization in adjacent, coupled cells.

RESULTS

We developed a theoretical model of intracellular Ca(2+) oscillations that includes the dynamics of the membrane potential controlled by the cyclic activation of Ca(2+)-activated K(+) channels. We found that membrane potential oscillations determine an in-phase oscillating Ca(2+) influx that significantly affects the amplitude, duration and oscillatory frequency of the intracellular Ca(2+) concentration oscillations. Under specific levels of hormone stimulation Ca(2+)-activated K(+) channels are essential for establishing or inhibiting the intracellular Ca(2+) concentration oscillatory activity, as also suggested by some experimental findings. We also found that in electrically coupled cells displaying Ca(2+)-activated K(+) channels-induced membrane potential oscillations, the synchronization of intracellular Ca(2+) concentration oscillations in adjacent cells can occur in the complete absence of gap junction Ca(2+) or inositol trisphosphate diffusion, the simple electrical coupling being sufficient for synchronization. Finally, electrical coupling between adjacent cells was found to work in synergy with gap junction Ca(2+) permeability in the synchronization of intracellular Ca(2+) concentration oscillations, making it to occur at lower gap junction Ca(2+) permeabilities.

CONCLUSIONS

Data from our model indicate that Ca(2+)-activated K(+) channel activity may be critical to establish important properties of the intracellular Ca(2+) concentration oscillations, and may help synchronize intracellular Ca(2+) concentration oscillations in electrically coupled cells. The model we propose here thus represents a third model of synchronization of intracellular Ca(2+) concentration oscillations in adjacent cells, based exclusively on the gap junction electrical coupling between cells displaying Ca(2+)-activated K(+) channel-induced membrane potential oscillations.