Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells

Abstract

-Although the numerous stimuli representing the taste quality of bitterness are known to be transduced through multiple mechanisms, recent studies have suggested an unpredicted complexity of the transduction pathways for individual bitter stimuli. To investigate this notion more thoroughly, a single prototypic bitter stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging techniques on dissociated rat taste receptor cells. At behaviorally relevant concentrations, caffeine produced strong inhibition of outwardly and inwardly rectifying potassium currents. Caffeine additionally inhibited calcium current, produced a weaker inhibition of sodium current, and was without effect on chloride current. Consistent with its effects on voltage-dependent currents, caffeine caused a broadening of the action potential and an increase of the input resistance. Caffeine was an effective stimulus for elevation of intracellular calcium. This elevation was concentration dependent, independent of extracellular calcium or ryanodine, and dependent on intracellular stores as evidenced by thapsigargin treatment. These dual actions on voltageactivated ionic currents and intracellular calcium levels suggest that a single taste stimulus, caffeine, utilizes multiple transduction mechanisms. sensory transduction; bitter; patch clamp; fura 2; ratiometric imaging TASTE RECEPTOR CELLS CONVEY gustatory information from the oral cavity to afferent nerve fibers that, in turn, relay their activation to the central nervous system. Our present understanding of these processes suggests that not only do different transduction mechanisms exist for the varying qualities of taste but multiple mechanisms exist within a taste quality (15,18). Bitter stimuli, in particular, comprise a particularly heterogeneous group of chemically diverse compounds. For example, alkaloids, glucosides, divalent cations, methylated or acetylated carbohydrates, amino acids, and dipeptides are reported to produce bitter sensations in humans. It is not surprising that a number of mechanisms might be required for this wide array of chemically diverse compounds. Moreover, because many bitter compounds are toxic, there exists an evolutionary advantage to evolve multiple mechanisms to sense noxious stimuli. The details of these transduction mechanisms are the subject of this study.Bitter stimuli have been proposed to utilize transduction pathways that include receptor-mediated production or inhibition of second-messenger molecules, modulation of second-messenger molecules by direct interaction with G proteins or degradative enzymes such as phosphodiesterase, or direct block of ion channels. Many bitter stimuli are proposed to be transduced via the gustducin pathway. Gustducin, a G protein expressed in 20-30% of taste receptor cells, shares considerable homology with transducin in photoreceptors (31). By analogy to transducin, the activation of gustducin by a seven-transmembrane receptor is suggested to stimulate phosphodiesterase, thereby lowering cyclic nucleotide...

Recent fat intake modulates fat taste sensitivity in lean and overweight subjects

“…While this is yet to be confirmed, within the oral cavity sensory adaptation (that is, a reduction in sensory response) within taste cells have been reported following prolonged or chronic stimulation with tastants. 12,13 In this paradigm, excess sensory stimulation leads to a decrease in sensory response, leading to an increase in the amount of sensory stimuli required to elicit an appropriate sensory response. In the context of obesity, where dietary fat consumption constitutes a salient environmental contributor, the mechanisms underpinning fat intake and how they manifest in the OB state are of particular interest.…”

Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels

“…More recently, phospholipase C␤ 2 (PLC␤ 2 ) and TRPM5, a member (melastatin subtype 5) of the transient receptor potential (TRP) family (49), have been linked to bitter and sweet signal transduction (55,56,81). There is evidence for the activation of multiple second messenger pathways and ion channels in individual taste cells (1,82). Clearly, taste signal transduction is complex and multifactorial and there is still much that is unknown about individual taste cell regulation.…”

Expression and characterization of delayed rectifying K+ channels in anterior rat taste buds

“…While K ϩ channels play a role in the action potential and the electrical excitability of the taste cell, they also have been implicated either directly or indirectly in a number of taste transduction pathways in the mammalian gustatory system. Inhibition of K ϩ channels, particularly DRK channels, has been demonstrated in response to acids (16,37), sweeteners (14,32), bitter tastants (65), and free fatty acids (26). While evidence for DRK channel inhibition by tastants in some cases is directly at the level of the channel (e.g., acids, fatty acids, some bitters), this effect may also be indirect, occurring through second-messenger cascades that ultimately result in the closure of DRK channels and depolarization.…”