Voltage-dependent calcium channels in mammalian motor synapses – triggers and modulators of neuromuscular transmission

The initiation of fast synchronous quantal release of neurotransmitters in central and peripheral synapses is ensured by a local increase in the concentration of Ca2+ ions in the nerve terminals near the Ca2+ sensors of synaptic vesicles in response to depolarization of the presynaptic membrane by an action potential (AP) propagating along the axon. The Ca2+- entry from the outside through presynaptic voltage-dependent Ca2+ channels CaV2.1 or CaV2.2 (P/Q- or N-type) is the main way of forming a dynamic Ca2+ signal that initiates the process of exocytosis of synaptic vesicles in virtually all types of chemical synapses and is capable of inducing the development of certain Ca2+-dependent forms of synaptic plasticity. However, in recent years it has become obvious that the set of sources and the spectrum of presynaptic Ca2+ signals are very diverse. Identification of the ensemble of regulatory Ca2+-entries operating in combination with their corresponding targets, description of their contribution to the mechanisms controlling quantal release of neurotransmitter is a topical area of modern synaptic physiology. Among such additional to the trigger Ca2+-inputs, L-type Ca2+-channels are of particular interest. Their role and activation conditions in neuromuscular junctions (NMJs) are poorly studied and do not provide an unambiguous idea of the place of this Ca2+-entry in the regulation of acetylcholine (ACh) release in vertebrate motor synapses. This review systematizes the currently available research results on the diverse functional role of voltage-gated Ca2+-channels in mammalian NMJs and presynaptic signaling pathways that control these Ca2+-inputs and their participation in the processes of fine-tuning the ACh quantal release.