Voltage-Dependent Calcium Channels in Mammalian Motor Synapses: Triggers and Modulators of Neuromuscular Transmission

The initiation of the fast synchronous quantal release ofneurotransmitters in central and peripheral synapses is ensuredby a local increase in the concentration of Ca²⁺ ionsin the nerve terminals near the Ca²⁺ sensorsof synaptic vesicles in response to depolarization of the presynapticmembrane by an action potential (AP) propagating along the axon.Ca²⁺ entry into the nerve terminal throughpresynaptic voltage-dependent Ca²⁺ channelsCa_V2.1 or Ca_V2.2 (P/Q-or N-type) is the main route to form a dynamic Ca²⁺ signalthat triggers the process of exocytosis of synaptic vesicles invirtually all types of chemical synapses and is able to induce thedevelopment of certain Ca²⁺-dependentforms of synaptic plasticity. However, in recent years it has becomeobvious that the set of sources and the spectrum of presynapticCa²⁺ signals are very diverse. Identificationof the ensemble of regulatory Ca²⁺ entriesco-operating with their targets, as well as characterization oftheir contribution to the mechanisms controlling quantal neurotransmitterrelease, is a topical area of modern synaptic physiology. Amongthe Ca²⁺ entries additional to thoseinvolved in triggering vesicular endocytosis, L-type Ca²⁺ channelsare of particular interest. Their function and activation conditionsin neuromuscular junctions (NMJs) are poorly studied, providingno unambiguous idea of the role of this Ca²⁺ entryin the regulation of acetylcholine (ACh) release in vertebrate motorsynapses. This review systematizes the currently available dataon the diverse functional role of voltage-gated Ca²⁺ channelsin mammalian NMJs and presynaptic signaling pathways that controlthese Ca²⁺-inputs and their implicationin the processes of fine-tuning ACh quantal release.