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Sci Signal. 2018 May 8;11(529). pii: eaao1815. doi: 10.1126/scisignal.aao1815.

Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.

Author information

1
Institute of Cell Biophysics, Russian Academy of Science, Pushchino, Moscow Region 142290, Russia.
2
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.
3
Immanuel Kant Baltic Federal University, Kaliningrad 236041, Russia.
4
Rocky Mountain Taste and Smell Center, Department of Cell and Developmental Biology, University Colorado School of Medicine, Aurora, CO 80045, USA.
5
Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
6
United Pushchino Center for Electron Microscopy, Pushchino, Moscow Region 142290, Russia.
7
Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
8
Department of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden.
9
Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, and 3D-Electron Microscopy, Renovo Neural Inc., Cleveland, OH 44195, USA.
10
Rocky Mountain Taste and Smell Center, Department of Biological Sciences, University of Denver, Denver, CO 80210, USA.
11
Institute of Cell Biophysics, Russian Academy of Science, Pushchino, Moscow Region 142290, Russia. tom.finger@ucdenver.edu staskolesnikov@yahoo.com.
12
Rocky Mountain Taste and Smell Center, Department of Cell and Developmental Biology, University Colorado School of Medicine, Aurora, CO 80045, USA. tom.finger@ucdenver.edu staskolesnikov@yahoo.com.

Abstract

Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which fuse with the plasma membrane to release neurotransmitters that activate postsynaptic receptors. In taste buds, type II receptor cells do not have conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP, through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry revealed that CALHM1 was localized to points of contact between the receptor cells and sensory nerve fibers. Ultrastructural and super-resolution light microscopy showed that the CALHM1 channels were consistently associated with distinctive, large (1- to 2-μm) mitochondria spaced 20 to 40 nm from the presynaptic membrane. Pharmacological disruption of the mitochondrial respiratory chain limited the ability of taste cells to release ATP, suggesting that the immediate source of released ATP was the mitochondrion rather than a cytoplasmic pool of ATP. These large mitochondria may serve as both a reservoir of releasable ATP and the site of synthesis. The juxtaposition of the large mitochondria to areas of membrane displaying CALHM1 also defines a restricted compartment that limits the influx of Ca2+ upon opening of the nonselective CALHM1 channels. These findings reveal a distinctive organelle signature and functional organization for regulated, focal release of purinergic signals in the absence of synaptic vesicles.

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