Light regulation of Ca²⁺ in the cone photoreceptor synaptic terminal

Retinal cones are depolarized in darkness, keeping voltage-gated Ca ²⁺ channels open and sustaining exocytosis of synaptic vesicles. Light hyperpolarizes the membrane potential, closing Ca²⁺ channels and suppressing exocytosis. Here, we quantify the Ca²⁺ concentration in cone terminals, with Ca²⁺ indicator dyes. Two-photon ratiometric imaging of fura-2 shows that global Ca²⁺ averages ∼360 nM in darkness and falls to ∼190 nM in bright light. Depolarizing cones from their light to their dark membrane potential reveals hot spots of Ca²⁺ that co-label with a fluorescent probe for the synaptic ribbon protein ribeye, consistent with tight localization of Ca²⁺ channels near ribbons. Measurements with a low-affinity Ca²⁺ indicator show that the local Ca²⁺ concentration near the ribbon exceeds 4 μM in darkness. The high level of Ca²⁺ near the ribbon combined with previous estimates of the Ca²⁺ sensitivity of release leads to a predicted dark release rate that is much faster than observed, suggesting that the cone synapse operates in a maintained state of synaptic depression in darkness.