Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli
Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli
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DOI：
10.1038/35098087
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发表时间：
2001-10-11
期刊：
影响因子：
64.8
通讯作者：
Lindemann, B
中科院分区：
文献类型：
--
作者：
Stevens, DR;Seifert, R;Lindemann, B
酸味是由作用于受体蛋白或通道的质子引起的。在脊椎动物中，这种味道质量的转导涉及几个平行的通路(1-5)。在这里，我们研究了酸刺激对大鼠瓦状乳头切片中味觉细胞的影响。从一组细胞中，我们发现了一种超极化激活电流，这种电流通过味孔的酸刺激而增强。这种电流类似于在神经元和心肌细胞中发现的Ih(6，7)，这种电流由超极化激活和环核苷酸门控(HCN)通道家族的成员携带(8-13)。我们通过原位杂交和免疫组织化学方法表明，HCN1和HCN4在味觉细胞亚群中表达。相比之下，参与苦味和甜味的G蛋白Gustducin在这些细胞中不表达。降低细胞外pH会使HCN通道的激活曲线呈剂量依赖的平坦化，并使半最大激活电压向更正的电压转变。我们的结果表明，HCN通道受细胞外质子的控制，可能是酸味的受体。
Sour taste is initiated by protons acting at receptor proteins or channels. In vertebrates, transduction of this taste quality involves several parallel pathways(1-5). Here we examine the effects of sour stimuli on taste cells in slices of vallate papilla from rat. From a subset of cells, we identified a hyperpolarization-activated current that was enhanced by sour stimulation at the taste pore. This current resembled Ih found in neurons and cardio-myocytes(6,7), a current carried by members of the family of hyperpolarization-activated and cyclic-nucleotide-gated (HCN) channels(8-13). We show by in situ hybridization and immunohistochemistry that HCN1 and HCN4 are expressed in a subset of taste cells. By contrast, gustducin, the G-protein involved in bitter and sweet taste(14), is not expressed in these cells. Lowering extracellular pH causes a dose-dependent flattening of the activation curve of HCN channels and a shift in the voltage of half-maximal activation to more positive voltages. Our results indicate that HCN channels are gated by extracellular protons and may act as receptors for sour taste.