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

Background informationIn many non-excitable cells hormone stimulation triggers repetitive oscillations of the intracellular Ca2+ concentration, thought to be important in several cell functions. Although most of these cells respond to an elevation of the intracellular Ca2+ concentration with a membrane hyperpolarization, due to the activation of Ca2+-activated K+ channels, theoretical models do not usually consider the contribution of the membrane potential dynamics in defining the properties of the intracellular Ca2+ concentration oscillations and their synchronization in adjacent, coupled cells.ResultsWe developed a theoretical model of intracellular Ca2+ oscillations that includes the dynamics of the membrane potential controlled by the cyclic activation of Ca2+-activated K+ channels. We found that membrane potential oscillations determine an in-phase oscillating Ca2+ influx that significantly affects the amplitude, duration and oscillatory frequency of the intracellular Ca2+ concentration oscillations. Under specific levels of hormone stimulation Ca2+-activated K+ channels are essential for establishing or inhibiting the intracellular Ca2+ concentration oscillatory activity, as also suggested by some experimental findings. We also found that in electrically coupled cells displaying Ca2+-activated K+ channels-induced membrane potential oscillations, the synchronization of intracellular Ca2+ concentration oscillations in adjacent cells can occur in the complete absence of gap junction Ca2+ 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 Ca2+ permeability in the synchronization of intracellular Ca2+ concentration oscillations, making it to occur at lower gap junction Ca2+ permeabilities.ConclusionsData from our model indicate that Ca2+-activated K+ channel activity may be critical to establish important properties of the intracellular Ca2+ concentration oscillations, and may help synchronize intracellular Ca2+ concentration oscillations in electrically coupled cells. The model we propose here thus represents a third model of synchronization of intracellular Ca2+ concentration oscillations in adjacent cells, based exclusively on the gap junction electrical coupling between cells displaying Ca2+-activated K+ channel-induced membrane potential oscillations.

► We developed a theoretical model of [Ca2+]i including the KCa channels activity. ► KCa channels significantly affects the main properties of [Ca2+]i oscillations. ► Under specific hormone stimulation they are essential for the oscillatory activity.► KCa channels could also synchronize [Ca2+]i oscillations in adjacent cells.