Amiloride inhibition on NaCl responses of the chorda tympani nerve in two 129 substrains of mice, 129P3/J and 129X1/SvJ
Amiloride inhibition on NaCl responses of the chorda tympani nerve in two 129 substrains of mice, 129P3/J and 129X1/SvJ
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DOI：
10.1093/chemse/bjj061
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发表时间：
2006-07-01
期刊：
影响因子：
3.5
通讯作者：
Ninomiya, Yuzo
中科院分区：
文献类型：
--
作者：
Ohkuri, Tadahiro;Yasumatsu, Keiko;Ninomiya, Yuzo
阿米洛利是一种钠通道阻滞剂，已知在各种哺乳动物中可以抑制鼓索(CT)神经的氯化钠反应。在小鼠中，据报道，阿米洛利对氯化钠的抑制作用因菌株而异。在C57BL小鼠中，阿米洛利抑制了大约50%的对照组的氯化钠反应，而在之前对129只小鼠的研究中，没有明显的抑制作用。然而，来自行为研究的证据并不完全符合这一点。最近，人们发现129只小鼠的遗传背景在不同的亚系之间存在差异。129X1/SVJ(以前的129/SVJ)小鼠与129P3/J(以前的129/J)品系相比，有25%的序列长度多态。因此，我们检测了129P3/J和129X1/SVJ小鼠在电生理阿米洛利敏感性方面可能存在的亚株差异。记录了对氯化钠的反应。在129P3/J和129X1/SVJ小鼠中，阿米洛利显著抑制CT对氯化钠的反应，而不影响对KCl的反应。然而，在129X1/SVJ小鼠中，阿米洛利抑制的幅度明显大于129P3/J小鼠(与对照对0.03-0.3M氯化钠和100mM阿米洛利的抑制幅度相似)(相当于对照组对0.01-1.0M氯化钠对100mU阿米洛利的反应的50%)。129P3/J小鼠抑制0.3M氯化钠反应的阈值浓度为30mU M，高于129X1/SVJ小鼠的10mU M。在129X1/SVJ小鼠中，引起盐反应抑制的阈值阿米洛利浓度和抑制程度与C57BL/6小鼠相似。这些结果表明，即使在129P3/J和129X1/SVJ这两个亚系之间，阿米洛利对氯化钠反应的敏感性也不同，129只小鼠的阿米洛利敏感性差异与两个近交系(129P3/J和C57BL/6)之间的差异一样大。
Amiloride, a sodium channel blocker, is known to suppress NaCl responses of the chorda tympani (CT) nerve in various mammalian species. In mice, the NaCl suppressing effect of amiloride is reported to differ among strains. In C57BL mice, amiloride inhibits NaCl responses to about 50% of control, whereas no such clear suppression was evident in prior studies with 129 mice. However, evidence from behavioral studies is not entirely consistent with this. Recently, it has been found that genetic backgrounds of 129 mice differ within substrains. 129X1/SvJ (formerly 129/SvJ) mice differ from the 129P3/J (formerly 129/J) strain by 25% of sequence length polymorphisms. Therefore, we examined possible substrain difference between 129P3/J and 129X1/SvJ mice in the amiloride sensitivity of electrophysiologically. recorded NaCl responses. Amiloride significantly suppressed CT responses to NaCl without affecting responses to KCl both in 129P3/J and 129X1/SvJ mice. However, the magnitude of the amiloride inhibition was significantly larger (similar to 50% of control in response to 0.01-1.0 M NaCl by 100 mu M amiloride) in 129X1/SvJ than in 129P3/J mice (similar to 20% of control in response to 0.03-0.3 M NaCl by 100 mu M amiloride). Threshold amiloride concentration for suppression of responses to 0.3 M NaCl was 30 mu M in 129P3/J mice, which was higher than that in 129X1/SvJ mice (10 mu M). In 129X1/SvJ mice, the threshold amiloride concentration eliciting inhibition of NaCl responses and the magnitude of the inhibition were comparable with those in C57BL/6 mice. These results suggest that amiloride sensitivity of NaCl responses differs even among the 129 substrains, 129P3/J and 129 X1/SvJ, and the substrain difference of 129 mice in amiloride sensitivity is as large as that between two inbred strains (129P3/J and C57BL/6).