Figure 8. Schematic model of mito-Ca²⁺ in developing and mature hair cells.

(A) In developing hair cells, spontaneous presynaptic-Ca²⁺ influx is linked to mito-Ca²⁺ uptake. Together these Ca²⁺ signals function to regulate ribbon size during ribbon formation. When the Ca_V1.3 or MCU channels are blocked, ribbon formation is increased leading to larger ribbons. These Ca²⁺ signals regulate ribbon formation via NAD(H) redox. MCU block lowers mito-Ca²⁺, increases the NAD⁺/NADH ratio and promotes ribbon formation. (B) In mature hair cells, evoked presynaptic-Ca²⁺ influx is linked to mito-Ca²⁺ uptake. When the MCU is partially blocked there is a reduction in presynaptic-Ca²⁺ influx. When the MCU is completely blocked there are synaptopathic consequences; ribbons are enlarged and synapses are lost.