Interactions between presynaptic Ca2+ channels, cytoplasmic messengers and proteins of the synaptic vesicle release complex

Influx of Ca2+ through presynaptic voltage-gated Ca2+ channels is a key step in rapid neurotransmitter release. The amount of Ca2+ entering through these channels is modulated by a plethora of intracellular messenger molecules, including beta gamma -subunits of G proteins, and protein kinases. In addition, Ca2+ channels bind physically to proteins of the vesicle-release machinery in a Ca2+ dependent manner; which can, in turn, regulate the activity of Ca2+ channels. Recent evidence suggests that second messengers and presynaptic vesicle-release proteins do not regulate Ca2+ channel activity as independent entities, but that there is extensive crosstalk between these two mechanisms. The complex interactions between second messengers, vesicle-release proteins and voltage-gated Ca2+ channels might provide multiple avenues for fine-tuning Ca2+ entry into the presynaptic terminal and, consequently, neurotransmission.