Impact of mitochondrial Ca²⁺ cycling on pattern formation and stability

Energization of mitochondria significantly alters the pattern of Ca²⁺ wave activity mediated by activation of the inositol (1,4,5) trisphosphate (IP₃) receptor (IP₃R) in Xenopus oocytes. The number of pulsatile foci is reduced and spiral Ca²⁺ waves are no longer observed. Rather, target patterns of Ca²⁺ release predominate, and when fragmented, fail to form spirals. Ca²⁺ wave velocity, amplitude, decay time, and periodicity are also increased. We have simulated these experimental findings by supplementing an existing mathematical model with a differential equation for mitochondrial Ca²⁺ uptake and release. Our calculations show that mitochondrial Ca²⁺ efflux plays a critical role in pattern formation by prolonging the recovery time of IP₃Rs from a refractory state. We also show that under conditions of high energization of mitochondria, the Ca²⁺ dynamics can become bistable with a second stable stationary state of high resting Ca²⁺ concentration.