Putative role of epithelial sodium channels (ENaC) in the afferent limb of cardio renal reflexes in rats
Putative role of epithelial sodium channels (ENaC) in the afferent limb of cardio renal reflexes in rats
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DOI：
10.1007/s00395-003-0426-7
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发表时间：
2003-11-01
影响因子：
9.5
通讯作者：
Veelken, R
中科院分区：
文献类型：
--
作者：
Ditting, T;Linz, P;Veelken, R
最近的研究表明，DEG/ENaC家族的离子通道在不同物种的机械感觉和大鼠的压力感受器反射控制中发挥作用。我们测试了心脏感觉网络中的ENaC对于机械感觉是强制性的这一假设。实验在雄性SD大鼠、分离的有心脏传入的结状神经节细胞和分离的迷走神经上进行。心外膜给药阿米洛利类似物苯扎米旨在特异性抑制位于心脏感觉传入的ENaC，确实以剂量依赖的方式钝化机械敏感性(即，静脉容量负荷对交感神经抑制的-32%和-42%，对照组为-67%；n=7；p<；0.05])以及-尽管程度较小-5-HT3介导的在体化学敏感的心或肾反射。然而，应用膜片钳技术发现，阿米洛利和苯扎米都不影响低渗应激刺激的结节神经节细胞的机械诱发电流。非特异性拉伸激活离子通道阻滞剂Gd完全消除机械诱导电流，表明各自的细胞是机械敏感的。在分离的迷走神经中，苯扎米使电刺激获得的动作电位受损(C峰幅度[-33%]；潜伏期[+12%]；n=8；p<；0.05)。我们的发现至少让人怀疑ENaC仅作为心脏感觉网络中的机械换能器发挥特殊作用。其他离子通道也可能参与其中。此外，体内观察到的结果也可能是由于传入信号传导的非特异性干扰。
Recent studies suggest a role of ion channels of the DEG/ENaC family for mechanosensation in different species and in baroreceptor reflex control in rats. We tested the hypothesis that ENaC within the cardiac sensory network are mandatory for mechanosensation. Experiments were performed in male Sprague-Dawley rats, isolated nodose ganglion cells with cardiac afferents and isolated vagus nerves.Epicardial delivery of the amiloride analogue benzamil intended to specifically inhibit ENaC presumably located on cardiac sensory afferents indeed blunted the mechanosensitive (i.e., sympathoinhibition by intravenous volume loading [-32% and -42% in treated groups vs. -67% in controls; n = 7 each; p < 0.05]) as well as - though to a lesser extent - the 5-HT3-mediated chemosensitive cardiorenal reflex in vivo in a dose-dependent manner. Using patch clamp technique, however, it turned out that neither amiloride nor benzamil influenced mechanically induced currents in ganglion nodosum cells in vitro, stimulated by hypoosmotic stress. The unspecific stretch activated ion channel blocker gadolinium completely abolished mechanically induced currents, indicating respective cells were mechanosensitive. In isolated vagus nerves benzamil impaired action potentials obtained by electrical stimulation (C-spike amplitude [-33%]; latency [+12%]; n = 8; p < 0.05).Our findings at least cast doubt on ENaC exclusively playing a specific role as mechanotransducers within the cardiac sensory network. Other ion channels might be involved. Furthermore the observed findings in vivo could also be due to unspecific disturbance of afferent signal conduction.