Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons
Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons
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DOI：
10.1152/ajpcell.00439.2005
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发表时间：
2006-02-01
影响因子：
5.5
通讯作者：
Simasko, SM
中科院分区：
文献类型：
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作者：
Peters, JH;Ritter, RC;Simasko, SM
我们以前报道过腹腔注射瘦素可以减少进食量，这依赖于完整的迷走神经传入。在胆囊收缩素（CCK）存在下，瘦素的这种作用增强。瘦素和CCK激活迷走神经传入神经元的机制尚不清楚。在本研究中，我们已经开始解决这个问题，通过使用膜片钳电生理技术来研究瘦素和CCK激活成年大鼠结状神经节培养的迷走神经传入的机制。我们发现，瘦素去极化41（60%）的68个神经元。膜去极化的幅度依赖于瘦素浓度，并发生在辣椒素敏感和辣椒素不敏感的神经元。我们还发现，大多数（16 22; 73%）的结状核神经元激活瘦素也敏感CCK。CCK诱导的去极化主要与内向电流的增加有关（11/12），而瘦素通过外向电流的减少（7/13）、内向电流的增加（3/13）或两者兼而有之（3/13）诱导背景电导的多种变化。然而，通过记录仅含钠或仅含钾的溶液进一步分离背景电流发现，瘦素和CCK都能够增加钠依赖性电导或抑制钾依赖性电导。我们的研究结果支持这一假设，迷走神经传入的收敛和整合点的瘦素和CCK信号控制的食物摄入量，并建议多种离子机制，瘦素和CCK激活迷走神经传入神经元。
We have previously reported that intraceliac infusion of leptin induces a reduction of meal size that depends on intact vagal afferents. This effect of leptin is enhanced in the presence of cholecystokinin (CCK). The mechanisms by which leptin and CCK activate vagal afferent neurons are not known. In the present study, we have begun to address this question by using patch-clamp electrophysiological techniques to examine the mechanisms by which leptin and CCK activate cultured vagal afferents from adult rat nodose ganglia. We found that leptin depolarized 41 (60%) of 68 neurons. The magnitude of membrane depolarization was dependent on leptin concentration and occurred in both capsaicin-sensitive and capsaicin-insensitive neurons. We also found that a majority (16 of 22; 73%) of nodose neurons activated by leptin were also sensitive to CCK. CCK-induced depolarization was primarily associated with the increase of an inward current (11 of 12), whereas leptin induced multiple changes in background conductances through a decrease in an outward current (7 of 13), an increase in an inward current (3 of 13), or both (3 of 13). However, further isolation of background currents by recording in solutions that contained only sodium or only potassium revealed that both leptin and CCK were capable of increasing a sodium-dependent conductance or inhibiting a potassium-dependent conductance. Our results support the hypothesis that vagal afferents are a point of convergence and integration of leptin and CCK signaling for control of food intake and suggest multiple ionic mechanisms by which leptin and CCK activate vagal afferent neurons.