Li Y W, Guyenet P G
Department of Pharmacology, Health Sciences Center, University of Virginia, Charlottesville 22908, USA.
Am J Physiol. 1997 Aug;273(2 Pt 2):R805-13. doi: 10.1152/ajpregu.1997.273.2.R805.
Sixty-two bulbospinal neurons were recorded in the rostral ventrolateral medulla (RVLM) of neonatal rats using patch electrodes. Sixty-one percent of the recorded neurons identified by histology contained tyrosine-hydroxylase (C1 cells). Substance P increased the spontaneous firing rate of all recorded cells but had no effect on spike configuration. The peptide depolarized neurons that were silenced by injection of hyperpolarizing current and increased their input resistance. All cells (n = 12) were activated by a neurokinin (NK)1 receptor agonist but most were unaffected by an NK2- or an NK2-selective compound. In voltage clamp, substance P produced a current that was linearly related to the membrane voltage. This current reversed polarity close to the potassium equilibrium potential in 11 of 23 cells. It reversed at more hyperpolarized potentials or not at all in the rest of the cells. In conclusion, substance P upregulates the intrinsic discharge rate of C1 and other putative sympathoexcitatory cells in neonatal rats. This effect is mediated via NK1 receptors. The depolarization is mediated by a reduction in resting potassium conductance and possibly by an additional cationic conductance. These results support the possibility that substance P could play a role "in vivo" in setting the basal level of discharge of the vasomotor cells of RVLM and therefore in regulating sympathetic vasomotor tone.
使用膜片电极在新生大鼠的延髓头端腹外侧区（RVLM）记录了62个延髓脊髓神经元。经组织学鉴定，所记录的神经元中有61%含有酪氨酸羟化酶（C1细胞）。P物质增加了所有记录细胞的自发放电频率，但对动作电位形态没有影响。该肽使因注入超极化电流而沉默的神经元去极化，并增加其输入电阻。所有细胞（n = 12）均被神经激肽（NK）1受体激动剂激活，但大多数细胞不受NK2或NK2选择性化合物的影响。在电压钳实验中，P物质产生的电流与膜电压呈线性相关。在23个细胞中的11个细胞中，该电流在接近钾平衡电位处反转极性。在其余细胞中，它在更超极化的电位处反转或根本不反转。总之，P物质上调新生大鼠C1细胞和其他假定的交感兴奋细胞的内在放电率。这种作用是通过NK1受体介导的。去极化是由静息钾电导降低介导的，可能还由额外的阳离子电导介导。这些结果支持P物质可能在“体内”设定RVLM血管运动细胞放电的基础水平，从而调节交感神经血管运动张力方面发挥作用的可能性。
