Chemical synapses without synaptic vesicles: purinergic neurotransmission via a CALHM1 channel-mitochondrial signalingcomplex

摘要

The synapse linking taste receptor cells to the taste nerves shows unusual functional properties suggestive of a unique structural organization. Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which upon activation, fuse to the plasma membrane to release neurotransmitter that activates receptors on the postsynaptic cell. In taste buds, taste receptor cells (Type II sensory cells) exhibit no conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP -- not via fusion of synaptic vesicles to the membrane but rather through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry reveals that CALHM1 is tightly localized to points of contact between the receptor cells and sensory nerve fibers. Ultrastructural and super-resolution light microscopy show that the CALHM1 channels always are associated with distinctive, large (1–2μm) mitochondria spaced 20–40 nm from the presynaptic membrane. Pharmacological disruption of the mitochondrial respiratory chain limits the ability of the taste cells to release ATP suggesting that the immediate source of released ATP is the mitochondrion rather than a global cytoplasmic pool of ATP. These large mitochondria may serve as both a reservoir of releasable ATP as well as the site of synthesis. The juxtaposition of the large mitochondrion to the areas of membrane displaying CALHM1 also define a restricted compartment that limits the influx of Ca²⁺ upon opening of the non-selective 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.