Light regulation of Ca2+ in the cone photoreceptor synaptic terminal

Retinal cones are depolarized in darkness. keeping voltage-gated Ca2+, 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 similar to 360 nM in darkness and falls to similar to 190 nM in bright light. Depolarizing cone 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 mu M 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.