Institute for Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, Giessen, Germany.
Pflugers Arch. 2019 Jul;471(7):1007-1023. doi: 10.1007/s00424-019-02276-1. Epub 2019 May 15.
Ion-transport properties of the epithelium of the cecum, the biggest fermental chamber in non-ruminant species, are largely unknown. Recently, in Ussing chamber experiments, segmental differences in basal short-circuit current (I) in rat corpus ceci were observed. The oral segment usually exhibited a much lower or even negative basal I in comparison with the aboral segment. The aim of the present study was the closer characterization of these differences. Basal I was inhibited by bumetanide and tetrodotoxin in both segments, whereas indomethacin reduced basal I only in the aboral corpus. Amiloride did not inhibit basal I suggesting that spontaneous anion secretion (but not electrogenic Na absorption via ENaC) contributes to the baseline current. In both segments, mucosally applied K channel blockers increased I indicating a spontaneous K secretion. Basolateral depolarization was used to characterize the ion conductances in the apical membrane. When a Cl gradient was applied, apical Cl conductance stimulated by carbachol and by forskolin was revealed. When the Cl gradient was omitted and instead a K gradient was used to drive currents across apical K channels, a Ba-sensititve K conductance was observed in both segments, and carbachol stimulated this conductance leading to a negative I. Conversely, forskolin induced a positive I under these conditions which was dependent on the presence of mucosal Na consistent with electrogenic Na absorption. This current was reduced by amiloride and several blockers of members of the TRP channel superfamily. These results indicate that similar transport mechanisms are involved in electrogenic ion transport across cecal oral and aboral segments, but with a higher spontaneous prostaglandin production in the aboral segment responsible for higher basal transport rates of both anions and cations.
盲肠是无反刍动物最大的发酵室,其黏膜上皮的离子转运特性在很大程度上尚未可知。最近,在 Ussing 腔室实验中观察到大鼠盲肠体段基础短路电流(I)存在节段性差异。与盲肠前段相比,盲肠后段的基础 I 通常较低,甚至为负值。本研究旨在更深入地描述这些差异。布美他尼和河豚毒素均可抑制两段的基础 I,而吲哚美辛仅在盲肠前段抑制基础 I。氨氯吡脒不抑制基础 I,提示自发阴离子分泌(而非 ENaC 介导的电中性 Na 吸收)对基础电流有贡献。在两段中,黏膜应用 K 通道阻滞剂均可增加 I,表明存在自发的 K 分泌。基底膜去极化用于描述顶端膜的离子电导。当应用 Cl 浓度梯度时,发现可被 carbachol 和 forskolin 刺激的顶端 Cl 电导。当省略 Cl 浓度梯度,而使用 K 浓度梯度驱动顶端 K 通道电流时,在两段中均观察到 Ba 敏感的 K 电导,carbachol 刺激该电导导致负性 I。相反,在这些条件下,forskolin 诱导正性 I,该电流依赖于黏膜 Na 的存在,与电中性 Na 吸收相关。这种电流被氨氯吡脒和几种 TRP 通道超家族成员的抑制剂所减少。这些结果表明,在电中性离子跨盲肠口腔段和盲肠前段的转运中涉及类似的转运机制,但盲肠前段的前列腺素生成更高,导致阴离子和阳离子的基础转运速率更高。