CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes.
Neuron
; 98(3): 547-561.e10, 2018 05 02.
Article
in En
| MEDLINE
| ID: mdl-29681531
ABSTRACT
Binding of sweet, umami, and bitter tastants to G protein-coupled receptors (GPCRs) in apical membranes of type II taste bud cells (TBCs) triggers action potentials that activate a voltage-gated nonselective ion channel to release ATP to gustatory nerves mediating taste perception. Although calcium homeostasis modulator 1 (CALHM1) is necessary for ATP release, the molecular identification of the channel complex that provides the conductive ATP-release mechanism suitable for action potential-dependent neurotransmission remains to be determined. Here we show that CALHM3 interacts with CALHM1 as a pore-forming subunit in a CALHM1/CALHM3 hexameric channel, endowing it with fast voltage-activated gating identical to that of the ATP-release channel in vivo. Calhm3 is co-expressed with Calhm1 exclusively in type II TBCs, and its genetic deletion abolishes taste-evoked ATP release from taste buds and GPCR-mediated taste perception. Thus, CALHM3, together with CALHM1, is essential to form the fast voltage-gated ATP-release channel in type II TBCs required for GPCR-mediated tastes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Taste
/
Calcium Channels
/
Ion Channel Gating
/
Receptors, Purinergic
/
Receptors, G-Protein-Coupled
/
Taste Perception
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Neuron
Journal subject:
NEUROLOGIA
Year:
2018
Document type:
Article