Histamine H-3 receptor-mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro
Histamine H-3 receptor-mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro
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DOI：
10.1113/jphysiol.1996.sp021675
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发表时间：
1996-10-01
影响因子：
5.5
通讯作者：
Reymann, KG
中科院分区：
文献类型：
--
作者：
Brown, RE;Reymann, KG
1.采用细胞外和全细胞膜片钳记录技术，观察组胺对大鼠海马齿状回兴奋性突触传递的影响。结果：1.在所有实验中，GABA(A)受体拮抗剂印防己毒素(50mU M)均存在于浴液中。组胺(0.7-70mU)细胞内记录的可逆性压低场兴奋性突触后电位(FEPSP)或兴奋性突触后电流(EPSCs)高达30%。谷氨酸受体激动剂S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸(S-AMPA)压力注射到脑片后，突触前纤维抽动和EPSC翻转电位不受组胺的影响。组胺(7 MM)对双组分EPSC的AMPA和N-甲基-D-天冬氨酸(NMDA)组分均有抑制作用，记录在-40 mV.3。除了抑制突触传递，组胺还降低了内侧穿支路径EPSC.5的成对脉冲抑制(PPD；脉冲间间隔40ms)的幅度。组胺对内侧穿孔通路EPSCs的抑制作用强于外侧穿孔通路EPSCs。组胺可增强侧支通路的双脉冲易化(PPP；脉冲间隔40ms)。组胺对突触传递和PPD的影响可被选择性H-3受体激动剂R-α-甲基组胺(0.1-10mU M)所模拟，但不能被选择性H-2受体激动剂迪马普特(10mU M)所模拟。同样，H-3受体拮抗剂硫代巴比妥钠(10 MU M)阻断组胺的作用，而H-1受体拮抗剂甲吡拉明(1 MU M)和H-2受体拮抗剂西咪替丁(50 MU M)则无效。代谢型谷氨酸激动剂L-2-氨基-4-膦酸丁酸酯不阻断组胺对突触传递和PPD的作用。结果表明，组胺通过与位于穿支通路终末的组胺H-3受体结合，抑制齿状回的突触传递。组胺抑制传递的机制独立于III类代谢性谷氨酸受体所使用的机制。
1. The effects of histamine on excitatory synaptic transmission in the dentate gyrus region of rat hippocampal slices were examined using extracellular and whole-cell patch-clamp recording techniques. The GABA(A) receptor antagonist picrotoxin (50 mu M) was present in the bath in all experiments.2. Histamine (0.7-70 mu M) reversibly depressed field excitatory postsynaptic potentials (fEPSPs) or excitatory postsynaptic currents (EPSCs) recorded intracellularly by up to 30%. The presynaptic fibre volley and EPSC reversal potential were unaffected by histamine, as were responses following pressure ejection of the glutamate receptor agonist S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S-AMPA) into the slice.3. Histamine (7 mu M) de-pressed equally the AMPA and N-methyl-D-aspartate (NMDA) components of the dual-component EPSC, recorded at -40 mV.4. In addition to depressing synaptic transmission, histamine also reduced the magnitude of paired-pulse depression (PPD; 40 ms interpulse interval) of the medial perforant path EPSC.5. Histamine depressed medial perforant path EPSCs more strongly than lateral perforant path EPSCs. Paired-pulse facilitation (PPP; 40 ms interpulse interval) in the lateral perforant path was enhanced by histamine.6. The effects of histamine on synaptic transmission and PPD were mimicked by the selective H-3 receptor agonist R-alpha-methylhistamine (0.1-10 mu M) but not by the selective H-2 receptor agonist dimaprit (10 mu M). Similarly, the H-3 receptor antagonist thioperamide (10 mu M) blocked the effect of histamine whereas the H-1 antagonist mepyramine (1 mu M) and the H-2 receptor antagonist cimetidine (50 mu M) n ere ineffective.7. Histamine actions on synaptic transmission and PPD were not occluded by application of the metabotropic glutamate agonist L-2-amino-4-phosphonobutyrate (AP4).8. The results indicate that histamine depresses synaptic transmission in the dentate gyrus by binding to histamine H-3 receptors located on perforant path terminals. The mechanism by which histamine depresses transmission is independent of that used by class III metabotropic glutamate receptors.