CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes

Abstract

Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of adenosine 5′-triphosphate (ATP), which acts as a neurotransmitter to activate afferent neural gustatory pathways1. However, how ATP is released to fulfill this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel2,3, is indispensable for taste stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas sour and salty taste recognition remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells to taste stimuli. Thus, CALHM1 is a voltage-gated ATP release channel required for sweet, bitter and umami taste perception.

Taste perception, associated hormonal modulation, and nutrient intake

“…[38][39][40] Increased intracellular calcium generated in response to tastant binding initiates membrane depolarization and the release of ATP via Calcium homeostasis modulator 1 (CALHM1) ion channels. 41,42 Type II cells also express voltage-gated sodium and potassium channels that mediate the secretion of ATP as a function of action potential firing rate. 43 Upon secretion, ATP acts as a neurotransmitter on nearby sensory afferent fibers 44,45 ; ATP also acts as a paracrine/autocrine hormone, binding with receptors expressed on neighboring taste receptor cells.…”

CALHM1 ion channel elicits amyloid-β clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain

“…These data strongly support the notion that Ca 2+ influx through CALHM1 is the trigger for the observed effect on Aβ clearance by IDE. It is important to note, however, that CALHM1 has been reported to form a large pore that can allow significant permeabilities for other ions, such as Na + , K + and Cl − , or for larger molecules, such as ATP (Ma et al, 2012;Siebert et al, 2013;Taruno et al, 2013). CALHM1 permeability activation is therefore expected to result in the control of multiple signaling pathways that could potentially also contribute to different mechanisms of IDE activation and to the observed effect on Aβ clearance.…”

“…Calhm1-KO mice were recently generated in our laboratory and are viable and fertile (Dreses-Werringloer et al, 2013;Ma et al, 2012;Taruno et al, 2013). Histological analyses have revealed that Calhm1 KO mice display no defects in brain development or brain integrity in adulthood (P.M. and V.V.…”

“…The Calhm1-KO mice were as described previously (Dreses-Werringloer et al, 2013;Taruno et al, 2013).…”

Progress and renewal in gustation: new insights into taste bud development

“…Type I cells express membrane-localized NTPDase2 (Entpd2), an ectoATPase that converts ATP to ADP. Type II cells use ATP as a neurotransmitter to signal to sensory nerves (Finger et al, 2005;Vandenbeuch et al, 2015), yet Type II cells lack presynaptic specializations; rather, Type II cells release ATP in a non-vesicular manner (Huang et al, 2007;Romanov et al, 2013Romanov et al, , 2007, probably via CALMH1 ion channels (Taruno et al, 2013). Thus, NTPDase2-expressing Type I cells are likely to clear excess ATP released by Type II cells to ensure efficient neurotransmission (Bartel et al, 2006;Finger et al, 2005;Vandenbeuch et al, 2013).…”