DeSimone J A, Lyall V, Heck G L, Phan T H, Alam R I, Feldman G M, Buch R M
Department of Physiology, Virginia Commonwealth University, Richmond, Virginia 23298-0551, USA.
J Neurophysiol. 2001 Nov;86(5):2638-41. doi: 10.1152/jn.2001.86.5.2638.
Chorda tympani taste nerve responses to NaCl can be dissected pharmacologically into amiloride-sensitive and -insensitive components. It is now established that the amiloride-sensitive, epithelial sodium channel acts as a sodium-specific ion detector in taste receptor cells (TRCs). Much less is known regarding the cellular origin of the amiloride-insensitive component, but its anion dependence indicates an important role for paracellular shunts in the determination of its magnitude. However, this has not precluded the possibility that undetected apical membrane ion pathways in TRCs may also contribute to its origin. Progress toward making such a determination has suffered from lack of a pharmacological probe for an apical amiloride-insensitive taste pathway. We present data here showing that, depending on the concentration used, cetylpyridinium chloride (CPC) can either enhance or inhibit the amiloride-insensitive response to NaCl. The CPC concentration giving maximal enhancement was 250 microM. At 2 mM, CPC inhibited the entire amiloride-insensitive part of the NaCl response. The NaCl response is, therefore, composed entirely of amiloride- and CPC-sensitive components. The magnitude of the maximally enhanced CPC-sensitive component varied with the NaCl concentration and was half-maximal at [NaCl] = 62 +/- 11 (SE) mM. This was significantly less than the corresponding parameter for the amiloride-sensitive component (268 +/- 71 mM). CPC had similar effects on KCl and NH(4)Cl responses except that in these cases, after inhibition with 2 mM CPC, a significant CPC-insensitive response remained. CPC (2 mM) inhibited intracellular acidification of TRCs due to apically presented NH(4)Cl, suggesting that CPC acts on an apical membrane nonselective cation pathway.
鼓索味觉神经对氯化钠的反应可通过药理学方法分解为对氨氯吡咪敏感和不敏感的成分。现已确定，对氨氯吡咪敏感的上皮钠通道在味觉受体细胞（TRCs）中充当钠特异性离子探测器。关于对氨氯吡咪不敏感成分的细胞起源知之甚少，但其对阴离子的依赖性表明细胞旁分流在其大小的确定中起重要作用。然而，这并未排除TRCs中未检测到的顶端膜离子途径也可能对其起源有贡献的可能性。由于缺乏针对顶端氨氯吡咪不敏感味觉途径的药理学探针，在做出这种确定方面的进展受到了阻碍。我们在此展示的数据表明，根据所使用的浓度，十六烷基氯化吡啶（CPC）可以增强或抑制对氯化钠的氨氯吡咪不敏感反应。产生最大增强作用的CPC浓度为250微摩尔。在2毫摩尔时，CPC抑制了氯化钠反应中整个对氨氯吡咪不敏感的部分。因此，氯化钠反应完全由对氨氯吡咪和CPC敏感的成分组成。最大增强的CPC敏感成分的大小随氯化钠浓度而变化，在[氯化钠]=62±11（标准误）毫摩尔时达到半数最大反应。这明显低于对氨氯吡咪敏感成分的相应参数（268±71毫摩尔）。CPC对氯化钾和氯化铵反应有类似影响，只是在这些情况下，用2毫摩尔CPC抑制后，仍有显著的对CPC不敏感的反应。CPC（2毫摩尔）抑制了由于顶端施加氯化铵导致的TRCs细胞内酸化，表明CPC作用于顶端膜非选择性阳离子途径。
