Figure 6

Effect of MCU activity on Ca²⁺ dynamics. \({[{{\rm{Ca}}}^{2+}]}_{{\rm{Cyt}}}^{{\rm{eff}}}\) oscillation frequency as a function of V_MCU is plotted for regions α (A) and β (B) with insets in each panel showing oscillations at two different values of V_MCU (indicated with colored arrows on the x-axis). Oscillations in region α were highly sensitive to changes in V_MCU (A), while in region β, frequency changed slightly with increasing V_MCU (B). Oscillatory cycles shown indicate that frequency is modulated primarily by the burst duration in region α (A inset), whereas it is modulated primarily by the duration of the interspike interval in region β (B inset). (C,D) Temporal changes in [Ca²⁺] are plotted for effective Cyt (black), Mt (cyan), and ER (red) following MCU KO (V_MCU = 0) and IP₃ stimulation (t = 50 s) in regions α (C) and β (D). (C) In region α, MCU KO resulted in loss of oscillations in all compartments. At steady-state, \({[{{\rm{Ca}}}^{2+}]}_{{\rm{Cyt}}}^{{\rm{eff}}}\) remained elevated and [Ca²⁺]_ER was slightly decreased compared to their corresponding basal levels. (D) In region β, MCU KO allowed for sustained \({[{{\rm{Ca}}}^{2+}]}_{{\rm{Cyt}}}^{{\rm{eff}}}\) and [Ca²⁺]_ER oscillations with increased amplitude compared to their corresponding control traces (Fig. 3B). Mt curves in either region show [Ca²⁺] depletion due to lack of Ca²⁺ influx (and continued Ca²⁺ efflux). Notice that [Ca²⁺]_Mt is multiplied by a factor of 10 (C,D).