Exocytosed protons feedback to suppress the Ca2+ current in mammalian cone photoreceptors

A proton pump acidifies synaptic vesicles and provides the electrochemical gradient for transmitter uptake. Although external protons can modulate membrane voltage- and ligand-gated conductances, the fate of the protons released when vesicles fuse with the plasma membrane is unclear. In the dark, the glutamate-laden vesicles of cone photoreceptors fuse continuously with the plasma membrane. I now show that vesicular protons feed back to block the nearby calcium channels that mediate release. This local proton-mediated feedback is a novel mechanism through which neurons may regulate the release of transmitter.