A model of intracellular Ca2+ oscillations based on the activity of the intermediate-conductance Ca2+-activated K+ channels Original Research Article

Intracellular Ca2+ oscillations are observed in a large number of non-excitable cells. While most appear to reflect an intermittent Ca2+ release from intracellular stores, in some instances intracellular Ca2+ oscillations strongly depend on Ca2+ influx, and are coupled to oscillations of the membrane potential, suggesting that a plasma membrane-based mechanism may be involved. We have developed a theoretical model for the latter type of intracellular Ca2+ oscillations based on the Ca2+-dependent modulation of the intermediate-conductance, Ca2+-activated K+ (IKCa) channel. The functioning of this model relies on the Ca2+-dependent activation, and the much slower Ca2+-dependent rundown of this channel. We have shown that Ca2+-dependent activation of the IKCa channels, the consequent membrane hyperpolarization and the resulting increase in Ca2+ influx may confer the positive feedback mechanism required for the ascending phase of the oscillation. The much slower Ca2+-dependent rundown process will conversely halt this positive loop, and establish the descending phase of the intracellular Ca2+ oscillation. We found that this simple model gives rise to intracellular Ca2+ oscillations when using physiologically reasonable parameters, suggesting that IKCa channels could participate in the generation of intracellular Ca2+ oscillations.