Resynthesis of phosphatidylinositol 4,5-bisphosphate mediates adaptation of the caffeine response in rat taste receptor cells

Caffeine, a prototypic bitter stimulus, produces several physiological actions on taste receptor cells that include inhibition of K_IR and K_V potassium currents and elevations of intracellular calcium. These responses display adaptation, i.e. their magnitude diminishes in the sustained presence of the stimulus. Levels of the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP₂) are well known to modulate many potassium channels, activating the channel by stabilizing its open state. Here we investigate a putative relationship of K_IR and K_V with PIP₂ levels hypothesizing that inhibition of these currents by caffeine might be allayed by PIP₂ resynthesis. Using standard patch-clamp techniques, recordings of either potassium current from rat posterior taste receptor cells produced essentially parallel results when PIP₂ levels were manipulated pharmacologically. Increasing PIP₂ levels by blocking phosphoinositide-3 kinase with wortmannin or LY294002, or by blocking phospholipase C with U73122 all significantly increased the incidence of adaptation for both K_IR and K_V. Conversely, lowering PIP₂ synthesis by blocking PI4K or using the PIP₂ scavengers polylysine or bovine serum albumin reduced the incidence of adaptation. Adaptation could be modulated by activation of protein kinase C but not calcium calmodulin kinase. Collectively, these data support two highly novel conclusions: potassium currents in taste receptor cells are significantly modulated by PIP₂ levels and PIP₂ resynthesis may play a central role in the gustatory adaptation process at the primary receptor cell level.