Presynaptic calcium channels: specialized control of synaptic neurotransmitter release

Abstract

Chemical synapses are heterogeneous junctions formed between neurons that are specialized for the conversion of electrical impulses into the exocytotic release of neurotransmitters. Voltage-gated Ca 2+ (Cav) channels play a pivotal role in this process as they are the major conduits for the Ca 2+ ions that trigger the fusion of neurotransmitter-containing vesicles with the presynaptic membrane. Alterations in the intrinsic function of these channels, and their positioning within the active zone can profoundly alter the timing and strength of synaptic output. Advances in optical and electron microscopic imaging, structural biology and molecular techniques have facilitated recent breakthroughs in our understanding of the properties of Cav channels that support their presynaptic functions. Here we examine the nature of these channels, how they are trafficked to and anchored within presynaptic boutons, and the mechanisms that allow them to function optimally in shaping the flow of information through neural circuits.

A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse

“…It is well established that the primary function of voltage-gated Ca v Ca 2+ channels within axon terminals is to serve as a conduit for Ca 2+ ions that trigger the fusion of neurotransmitter-laden vesicles with the presynaptic membrane (reviewed in Dolphin and Lee, 2020 ). Mutations in genes encoding presynaptic Ca v channels cause neurological disorders such as epilepsy, migraine, and ataxia ( Pietrobon, 2010 ).…”

“…Analyses of Ca v knockout (KO) mice have helped illuminate the physiological functions of Ca v channels ( Pietrobon, 2005 ), however, this approach does not distinguish between the Ca 2+ -dependent and Ca 2+ -independent contributions of these channels. Moreover, complex double and triple-KO approaches are needed given that most synapses in the nervous system utilize more than one Ca v subtype ( Dolphin and Lee, 2020 ).…”

Dendrimers as Modulators of Brain Cells

“…In the resting state, Ca 2+ concentrations are often between 50 and 100 nM, but they increase 10–100-fold when neurons are activated. Ca 2+ pulses regulate the structure and function of synapses and dendritic excitability [ 14 , 15 , 16 , 17 ]. The diffusion of signaling molecules is efficient at the micrometer scale and plays a critical role in signaling activities.…”

The mammalian rod synaptic ribbon is essential for Cavchannel facilitation and ultrafast fusion of the readily releasable pool of vesicles

“…A feature that sets Ca v 1.4 channels apart from other L-type channels is that their expression is limited to photoreceptor terminals (for review, McRory et al, 2004;Pangrsic et al, 2018). By comparison, other L-type channels, such as Ca v 1.2 and 1.3, are expressed throughout the nervous system, and additionally in cardiac, endocrine and neuroendocrine cells, and such prevalence has led to significantly more insight into their biophysical properties (Dolphin and Lee, 2020). Therefore, some of the basic biophysical properties of mouse rod Ca v 1.4 channels, which have not previously been described, are reported next.…”