Objective To investigate the effect of D-AP5 (D-2-amino-5-phosphonopentanoate, a specific NMDA-antagonist) on the increase of intracellular free Ca 2+ concentration ([Ca 2+ ] i) induced by glutamate in isol...
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Objective To investigate the effect of D-AP5 (D-2-amino-5-phosphonopentanoate, a specific NMDA-antagonist) on the increase of intracellular free Ca 2+ concentration ([Ca 2+ ] i) induced by glutamate in isolated cochlear inner hair cells (IHCs), and to detect the autoreceptors of the IHC membrane. Methods When a laser scanning confocal microscope (LSCM) was used, the exogenous glutamate (Glu)-induced changes in [Ca 2+ ] i of isolated IHCs and OHCs of guinea pig cochlea were observed with fluo-3, a fluorescent probe for [Ca 2+ ] i. After D-AP5 or CNQX (6--cyano--7--nitroguinoxaline--2, 3--dione, a specific AMPA- antagonist) was administrated, the exogenous glutamate (Glu)-induced changes in [Ca 2+ ] i of isolated IHCs were recorded. Results In the presence of a low concentration Glu (3.85?μmol/L), there was an increase of [Ca 2+ ] i in IHCs, whereas there was no change in OHCs. When 50?μmol/L of D-AP5 was administrated in advance, Glu did not induce a corresponding increase in [Ca 2+ ] i in IHCs, and 50?μmol/L of CNQX did not completely block the increase of [Ca 2+ ] i in IHCs. Conclusions These results suggest that the autoreceptors existing in the IHC membrane are mainly of NMDA type, while there are relatively few AMPA receptors. Exogenous Glu is capable of increasing [Ca 2+ ] i in IHCs by acting on the NMDA autoreceptor of IHCs in a positive feedback manner.
目的观察圆窗局部灌注泊洛沙姆407对耳蜗功能和结构的影响。方法 16只健康豚鼠右耳圆窗灌注100μl 20%泊洛沙姆407溶液作为实验组,左耳灌注生理盐水作为对照组,另取4只动物不予处理作为阴性对照组。于灌注前、后及灌注后第7、14、28及49 d 行听性脑干诱发电位(auditory brainstem response,ABR)检测,并于检测后分别处死4只动物,行耳蜗基底膜铺片并计数。结果泊洛沙姆407灌注后 ABR 阈值较灌注前均有所提高,但在49 d 时恢复至灌注前水平;耳蜗毛细胞计数显示泊洛沙姆407圆窗灌注后无明显毛细胞缺失。结论泊洛沙姆407圆窗灌注对 ABR阈值有暂时性影响,但未对耳蜗功能和结构起到持久性不可逆性损伤,符合中、内耳疾病的缓释给药治疗的条件。
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