Aosaki T, Kawaguchi Y
Laboratory for Neural Circuits, Institute of Physical and Chemical Research (RIKEN), Aichi, Japan.
J Neurosci. 1996 Aug 15;16(16):5141-53. doi: 10.1523/JNEUROSCI.16-16-05141.1996.
Actions of substance P (SP) on the neostriatal neurons in in vitro rat slice preparations were studied via whole-cell patch-clamp recording. Almost all large aspiny neurons (cholinergic cells) and half of the low-threshold spike (LTS) cells (somatostatin/ NOS-positive cells) showed depolarization or an inward shift of the holding currents in response to bath-applied SP in a dose-dependent manner. In contrast, no responses were observed in fast-spiking (FS) cells (parvalbumin-positive cells) and medium spiny cells. Spike discharges followed by slow EPSPs/EPSCs were evoked by intrastriatal electrical stimulation in the large aspiny neurons. Pretreatment with [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP, an antagonist of the SP receptor, reversibly suppressed the induction of the slow EPSPs/EPSCs and unmasked slow IPSCs. The SP-induced inward current, although almost unchanged even after the blockade of Ih channels and voltage-dependent Na+, Ca2+, and K+ channels, changed its amplitude according to the Na+ concentration used in both the large aspiny neurons and LTS cells. Thus, the cation current could account for virtually all of the inward current at resting levels in both neurons. These results suggest that the firing of afferent neurons such as striatonigral medium spiny neurons, one of the possible sources of SP, would increase the firing probability of the two types of interneurons of the neostriatum by SP-receptor-mediated opening of tetrodotoxin-insensitive cation channels.
通过全细胞膜片钳记录研究了P物质（SP）对体外大鼠脑片制备中的新纹状体神经元的作用。几乎所有的大无棘神经元（胆碱能细胞）和一半的低阈值棘波（LTS）细胞（生长抑素/一氧化氮合酶阳性细胞）在浴加SP后均呈现剂量依赖性的去极化或钳制电流内向偏移。相反，在快发放（FS）细胞（小白蛋白阳性细胞）和中等棘状细胞中未观察到反应。在大无棘神经元中，纹状体内电刺激诱发了随后伴有缓慢兴奋性突触后电位/兴奋性突触后电流的动作电位发放。用SP受体拮抗剂[D-Arg1，D-Pro2，D-Trp7,9，Leu11]-SP预处理可可逆性抑制缓慢兴奋性突触后电位/兴奋性突触后电流的诱导，并揭示出缓慢抑制性突触后电流。尽管在阻断Ih通道以及电压依赖性钠、钙和钾通道后，SP诱导的内向电流几乎不变，但在大无棘神经元和LTS细胞中，其幅度会根据所用的钠浓度而改变。因此，阳离子电流几乎可以解释这两种神经元静息水平下的所有内向电流。这些结果表明，诸如纹状体黑质中等棘状神经元等传入神经元的放电，作为SP的可能来源之一，将通过SP受体介导的河豚毒素不敏感阳离子通道的开放增加新纹状体两种中间神经元的放电概率。
