Browning Kirsteen N, Coleman F Holly, Travagli R Alberto
Dept. of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Am J Physiol Gastrointest Liver Physiol. 2005 Aug;289(2):G209-19. doi: 10.1152/ajpgi.00560.2004. Epub 2005 Apr 7.
We investigated the pre- and postsynaptic effects of pancreatic polypeptide (PP) on identified pancreas-projecting neurons of the rat dorsal motor nucleus of the vagus in thin brain stem slices. Perfusion with PP induced a TTX- and apamin-sensitive, concentration-dependent outward (22% of neurons) or inward current (21% of neurons) that was accompanied by a decrease in input resistance; PP was also found to affect the amplitude of the action potential afterhyperpolarization. The remaining 57% of neurons were unaffected. PP induced a concentration-dependent inhibition in amplitude of excitatory (n = 22 of 30 neurons) and inhibitory (n = 13 of 17 neurons) postsynaptic currents evoked by electrical stimulation of the adjacent nucleus of the solitary tract, with an estimated EC(50) of 30 nM for both. The inhibition was accompanied by an alteration in the paired pulse ratio, suggesting a presynaptic site of action. PP also decreased the frequency, but not amplitude, of spontaneous excitatory (n = 6 of 11 neurons) and inhibitory currents (n = 7 of 9 neurons). In five neurons, chemical stimulation of the area postrema (AP) induced a TTX-sensitive inward (n = 3) or biphasic (outward and inward) current (n = 2). Superfusion with PP reversibly reduced the amplitude of these chemically stimulated currents. Regardless of the PP-induced effect, the vast majority of responsive neurons had a multipolar somata morphology with dendrites projecting to areas other than the fourth ventricle or the central canal. These results suggest that pancreas-projecting rat dorsal motor nucleus of the vagus neurons are heterogeneous with respect to their response to PP, which may underlie functional differences in the vagal modulation of pancreatic functions.
我们在薄脑干切片中研究了胰多肽(PP)对大鼠迷走神经背核中已鉴定的胰腺投射神经元的突触前和突触后效应。用PP灌注可诱导出一种对河豚毒素(TTX)和蜂毒明肽敏感的、浓度依赖性的外向电流(占神经元的22%)或内向电流(占神经元的21%),同时伴有输入电阻降低;还发现PP会影响动作电位后超极化的幅度。其余57%的神经元未受影响。PP对电刺激相邻孤束核诱发的兴奋性突触后电流(30个神经元中的22个)和抑制性突触后电流(17个神经元中的13个)的幅度产生浓度依赖性抑制,两者的半数有效浓度(EC50)估计均为30 nM。这种抑制伴随着成对脉冲比率的改变,提示作用于突触前位点。PP还降低了自发性兴奋性突触后电流(11个神经元中的6个)和抑制性突触后电流(9个神经元中的7个)的频率,但不影响其幅度。在5个神经元中,化学刺激最后区(AP)可诱导出对TTX敏感的内向电流(3个)或双相电流(外向和内向,2个)。用PP灌流可使这些化学刺激电流的幅度可逆性降低。无论PP诱导何种效应,绝大多数反应性神经元具有多极胞体形态,其树突投射到第四脑室或中央管以外的区域。这些结果表明,大鼠迷走神经背核中胰腺投射神经元对PP的反应具有异质性,这可能是迷走神经对胰腺功能调节中功能差异的基础。