Kato K, Clifford D B, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Neuroscience. 1993 Mar;53(1):39-47. doi: 10.1016/0306-4522(93)90282-k.
Factors involved in the production of long-term potentiation in the CA1 region of rat hippocampal slices were examined using whole-cell voltage clamp recordings. The pairing of postsynaptic membrane depolarization with tetanic stimulation produced a reliable long-lasting enhancement of synaptic currents provided that the pairing was performed within 15 min after establishing intracellular contact. This time could be extended to 30 min by including adenosine triphosphate and guanosine triphosphate in the recording pipette. Once established, the potentiation persisted for 3 h or more. The washout of long-term potentiation generating ability was not correlated with a rundown in baseline synaptic currents or in the N-methyl-D-aspartate receptor-mediated component of synaptic responses, but followed a time course similar to the loss of calcium spikes. Long-term potentiation could be reliably produced by depolarizing the postsynaptic membrane to -40 or -20 mV during the tetanus, but decreased when the membrane was held at membrane potentials greater than 0 mV. At -20 mV, 50 microM 2-amino-5-phosphonovalerate blocked the potentiation but this agent was ineffective at +40 mV. In contrast, 50 microM verapamil, a calcium channel blocker, failed to alter long-term potentiation at -20 mV but blocked the enhancement at +40 mV. These results suggest that whole-cell recording causes a washout of postsynaptic factors important in the initiation of long-term potentiation. However, these factors are less important in maintaining the potentiation. Furthermore, depending on the postsynaptic membrane potential during tetanic stimulation, voltage-gated calcium channels contribute to CA1 long-term potentiation.
使用全细胞电压钳记录技术，研究了大鼠海马切片CA1区产生长时程增强（LTP）的相关因素。只要在建立细胞内接触后的15分钟内进行配对，将突触后膜去极化与强直刺激配对，就能可靠地产生突触电流的持久增强。通过在记录电极内加入三磷酸腺苷（ATP）和三磷酸鸟苷（GTP），这个时间可以延长到30分钟。一旦建立，这种增强可持续3小时或更长时间。长时程增强产生能力的消退与基线突触电流或突触反应中N-甲基-D-天冬氨酸（NMDA）受体介导成分的减少无关，而是遵循与钙峰丢失相似的时间进程。在强直刺激期间将突触后膜去极化到-40或-20 mV能可靠地产生长时程增强，但当膜电位保持在大于0 mV时，增强作用会减弱。在-20 mV时，50 μM的2-氨基-5-磷酸戊酸（APV）能阻断增强作用，但该药物在+40 mV时无效。相反，50 μM的钙通道阻滞剂维拉帕米在-20 mV时未能改变长时程增强，但在+40 mV时阻断了增强作用。这些结果表明，全细胞记录导致了对长时程增强起始重要的突触后因素的洗脱。然而，这些因素在维持增强作用方面不太重要。此外，根据强直刺激期间的突触后膜电位，电压门控钙通道对CA1区的长时程增强有贡献。
