A novel pharmacological probe links the amiloride-insensitive NaCl, KCl, and NH4Cl chorda tympani taste responses

Chorda tympani taste nerve responses to NaCl can be dissected pharmacologic ally into amiloride-sensitive and -insensitive components. It is now establ ished that the amiloride-sensitive, epithelial sodium channel acts as a sod ium-specific ion detector in taste receptor cells (TRCs). Much less is know n regarding the cellular origin of the amiloride-insensitive component, but its anion dependence indicates an important role for paracellular shunts i n the determination of its magnitude. However, this has not precluded the p ossibility that undetected apical membrane ion pathways in TRCs may also co ntribute to its origin. Progress toward making such a determination has suf fered from lack of a pharmacological probe for an apical amiloride-insensit ive taste pathway. We present data here showing that, depending on the conc entration used, cetylpyridinium chloride (CPC) can either enhance or inhibi t the amiloride-insensitive response to NaCl. The CPC concentration giving maximal enhancement was 250 muM. At 2 mM, CPC inhibited the entire amilorid e-insensitive part of the NaCl response. The NaCl response is, therefore, c omposed entirely of amiloride- and CPC-sensitive components. The magnitude of the maximally enhanced CPC-sensitive component varied with the NaCl conc entration and was half-maximal at [NaCl] = 62 +/- 11 (SE) mM. This was sign ificantly less than the corresponding parameter for the amiloride- sensitiv e component (268 +/- 71 mM). CPC had similiar effects on KCl and NH4Cl resp onses except that in these cases, after inhibition with 2 mM CPC, a signifi cant CPC-insensitive response remained. CPC (2 mM) inhibited intracellular acidification of TRCs due to apically presented NH4Cl, suggesting that CPC acts on an apical membrane nonselective cation pathway.