Dense core vesicles

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Chromaffin granules, platelet dense core vesicles, and synaptic vesicles accumulate ATP. ATP uptake has been demonstrated using chromaffin granules and synaptic vesicles and the process appears to depend on A(.lh+. It has generally been assumed that ATP is costored only with monoamines and acetylcholine, as an anion to balance to cationic charge of those transmitters. However, the extent of ATP storage and release by different neuronal populations remains unknown, and the proteins responsible for ATP uptake by secretory vesicles have not been identified. 

Figure 4.10 An electron micrograph of a terminal varicosity containing a large dense-core vesicle (LDCV), indicated by the arrow and many small synaptic vesicles (SSVs), some of which contain an electron dense core. Calibration mark 250 nM. (Figure kindly supplied by M. Fillenz)...

Winkler, H (1993) The adrenal chromaffin granule a model for larger dense core vesicles of endocrine and nervous tissue. J. Anat. 183 237-252. 

FIGURE 1-8 A dendrite (D) emerging from a motor neuron in the anterior horn of a rat spinal cord is contacted by four axonal terminals terminal 1 contains clear, spherical synaptic vesicles terminals 2 and 3 contain both clear, spherical and dense-core vesicles (arrow) and terminal 4 contains many clear, flattened (inhibitory) synaptic vesicles. Note also the synaptic thickenings and, within the dendrite, the mitochondria, neurofilaments and neurotubules. x33,000. 

Neuropeptides are packaged into large, dense-core vesicles 325 Diversity is generated by families of propeptides, alternative splicing, proteolytic processing and post-translational modifications 326... 

The neuropeptides exhibit a few key differences from the classical neurotransmitters. First, neuropeptides are present in tissues at much lower concentrations than classical neurotransmitters. Consistent with this, neuropeptides are also active at receptors at correspondingly lower concentrations. For example, the concentration of ACh and NE in synaptic vesicles is in the 100-500 mmol/1 range, while the concentration of neuropeptide in a large dense core vesicle is 3-10 mmol/1 at most. Correspondingly, the affinity of ACh for its receptors is in the micromolar to millimolar range, while peptides typically bind to their receptors with affinities in the nanomolar to micromolar range. 

FIGURE 1 8-3 Intracellular pathway of bioactive peptide biosynthesis, processing and storage. Neuropeptide precursors are synthesized on ribosomes at the endoplasmic reticulum and processed through the Golgi. Axonal transport of the large dense-core vesicle to the synaptic site of release precedes the actual secretion. 

FIGURE18-4 Neuropeptides and conventional neurotransmitters are released from different parts of the nerve terminal. A neuromuscular junction containing both large dense-core vesicles (containing the neuropeptide SCP) and also small synaptic vesicles (containing acetylcholine) was stimulated for 30 min at 12 Hz (3.5 s every 7 s). Depletion of the small clear vesicles at the muscle face and of the peptide granules at the nonmuscle face of the nerve terminal was observed. After stimulation, there was an increase in the number of large dense-core vesicles within one vesicle diameter of the membrane. (Adapted from reference [37].)... 

FIGURE 18-11 Regulation of neuropeptide expression is exerted at several levels. ER, endoplasmic reticulum LDCV, large dense-core vesicle TGN, trans-Golgi network. 

FIGURE 18-12 The/af//af mutation in carboxypeptidase E (CPE) leads to secretion of proinsulin, not mature insulin, and results in diabetes. The S202P mutation within CPE results in degradation of the enzyme and defective insulin processing in the fat/fat heterozygous mouse. LDCV, large dense-core vesicle. 

LDCV large dense core vesicle MTI magnetization-transfer imaging... 

Figure 17.1. Neurotransmission (specific case of peptidergic cells). Production of the peptides in the cel I body (1). Packing of the peptides i nto large dense core vesicles for further transport to the axons (2). Release of neuropeptides from the cell soma (3) dendrites (4) and outside of the synapse (5). Release of classic neurotransmitters in the synaptic cleft (6). G-protein-coupled type receptors, which act as peptide receptors. (See color insert.)...

The terminals of cholinergic neurons contain large numbers of small membrane-bound vesicles concentrated near the synaptic portion of the cell membrane (Figure 6-3) as well as a smaller number of large dense-cored vesicles located farther from the synaptic membrane. The large vesicles contain a high concentration of peptide cotransmitters (Table 6-1), while the smaller clear vesicles contain most of the acetylcholine. Vesicles are initially synthesized in the neuron soma and transported to the terminal. They may also be recycled several times within the terminal. 

Ca2+-Induced Exocytosis of Small Dense-Core Vesicles and LDCVs. 18... 

Monoaminergic neurotransmitters (dopamine, noradrenaline, adrenaline, histamine, and serotonin) are released by exocytosis of small dense-core vesicles from... 

Neuropeptides are secreted by exocytosis of large dense-core vesicles (LDCVs) outside of synapses (Figure 1 Salio et al., 2006). LDCVs undergo exocytosis in all parts of a neuron, most often in axon terminals and dendrites. Monoamines are often co-stored with neuropeptides in LDCVs and co-secreted with them upon exocytosis. For all intents and purposes, LDCV-mediated secretion resembles hormone secretion in endocrine cells. 

Philos Trans R Soc Lond B Biol Sd 354 337-46 Khvotchev M, Lonart G, Sudhof TC (2000) Role of caldum in neurotransmitter release evoked by alpha-latrotoxin or hypertonic sucrose. Neuroscience 101 793-802 Klenchin VA, Kowalchyk JA, Martin TF (1998) Large dense-core vesicle exocytosis in PC12 cells. Methods 16 204-8... 

Pickel, V. M, Chan, J., Veznedaroglu, E., and Milner, T. A. (1995). Neuropeptide Y and dynorphin-immunoreactive large dense-core vesicles are strategically localized for presynaptic modulation in the hippocampal formation and substantia nigra. Synapse 19, 160-169. 

---