Lateral Mobility of Presynaptic L-Type Calcium Channels at Photoreceptor Ribbon Synapses

At most synapses, presynaptic Ca2+ channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca2+ channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma tigrinum) retina. Movements of individual Ca2+ channels were tracked by coupling quantum dots to an antibody against the extracellular alpha(2)delta(4) Ca2+ channel subunit. alpha(2)delta(4) antibodies labeled photoreceptor terminals and colocalized with antibodies to synaptic vesicle glycoprotein 2 and voltage-gated Ca2+ channel 1.4 (Ca(V)1.4) alpha(1) subunits. The results show that Ca2+ channels are dynamic and move within a confined region beneath the synaptic ribbon. The size of this confinement area is regulated by actin and membrane cholesterol. Fusion of nearby synaptic vesicles caused jumps in Ca2+ channel position, propelling them toward the outer edge of the confinement domain. Channels rebounded rapidly toward the center. Thus, although Ca-V channels are mobile, molecular scaffolds confine them beneath the ribbon to maintain neurotransmission even at high release rates.