How do taste cells lacking synapses mediate neurotransmission? CALHM1, a voltage-gated ATP channel

Abstract

CALHM1 was recently demonstrated to be a voltage-gated ATP-permeable ion channel and to serve as a bona fide conduit for ATP release from sweet-, umami-, and bitter-sensing type II taste cells. Calhm1 is expressed in taste buds exclusively in type II cells and its product has structural and functional similarities with connexins and pannexins, two families of channel protein candidates for ATP release by type II cells. Calhm1 knockout in mice leads to loss of perception of sweet, umami, and bitter compounds and to impaired gustatory nerve responses to these tastants. These new studies validate the concept of ATP as the primary neurotransmitter from type II cells to gustatory neurons. Furthermore, they identify voltage-gated ATP release through CALHM1 as an essential molecular mechanism of ATP release in taste buds. We discuss these new findings, as well as unresolved issues in peripheral taste signaling that we hope will stimulate future research.

Keywords: ATP; TRPM5; calcium; connexin; pannexin; sensory; voltage-gated.

Figure 1

Scheme of taste signal transduction cascade in sweet, bitter, and umami type II taste cells. CALHM1 is an integral component of the ATP release channel, while contributions of pannexin 1 (PANX1) and connexins are still in question, as indicated by the question marks.

Figure 2

Shared and distinct structural properties of CALHM1, pannexin-1, innexin-1, and connexin43. Schematic depiction of the alignment of the secondary structures. Conserved cysteines and N-linked glycosylation sites are also shown.