New Insights Into Interactions of Presynaptic Calcium Channel Subtypes and SNARE Proteins in Neurotransmitter Release

Abstract

Action potential (AP) induces presynaptic membrane depolarization and subsequent opening of Ca2+ channels, and then triggers neurotransmitter release at the active zone of presynaptic terminal. Presynaptic Ca2+ channels and SNARE proteins (SNAREs) interactions form a large signal transfer complex, which are core components for exocytosis. Ca2+ channels serve to regulate the activity of Ca2+ channels through direct binding and indirect activation of active zone proteins and SNAREs. The activation of Ca2+ channels promotes synaptic vesicle recruitment, docking, priming, fusion and neurotransmission release. Intracellular calcium increase is a key step for the initiation of vesicle fusion. Various voltage-gated calcium channel (VGCC) subtypes exert different physiological functions. Until now, it has not been clear how different subtypes of calcium channels integrally regulate the release of neurotransmitters within 200 μs of the AP arriving at the active zone of synaptic terminal. In this mini review, we provide a brief overview of the structure and physiological function of Ca2+ channel subtypes, interactions of Ca2+ channels and SNAREs in neurotransmitter release, and dynamic fine-tune Ca2+ channel activities by G proteins (Gβγ), multiple protein kinases and Ca2+ sensor (CaS) proteins.

Analgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins

“…There is evidence that 2-1 interacts with several other proteins in brain (Table 2), although many of these interactions are very likely indirect, particularly those involving presynaptic vesicle release proteins that are known to directly interact with calcium channel 1 subunits (reviewed in: He et al, 2018).…”

Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

“…Ca V 2 channels interact with soluble N-ethylmaleimide-sensitive fusion protein receptors (SNAREs), which promote the fusion of secretory vesicles to the membrane in a calcium-dependent manner. This calcium generally enters through Ca V 2 channels [80].…”

Exacerbation of Stiff Person Syndrome by Selective Serotonin Reuptake Inhibitors

“…10 P/Q type channels belong to a subgroup of high voltage-activated calcium channels and have an important role in neurotransmitter release, similar to N-type VGCCs. 11 It is unclear why other medications acting through the N-type blockade (eg, gabapentin) may provide relief in patients with SPS. P/Q channels in the axon terminal are located closer to the release zone in comparison to other calcium channels in synapses.…”

“…P/Q channels in the axon terminal are located closer to the release zone in comparison to other calcium channels in synapses. 11 This may lead to a higher presynaptic concentration of calcium and co-localization with synaptotagmin-containing vesicle clusters. 11 This is in contrast to only partial involvement of N-type channels in vesicle clusters.…”