Coupling of L type calcium channels with ryanodine receptors in presynaptic nerve terminals

采用全细胞膜片钳技术，观察了在无钙条件下，钾离子诱导的突触前去极化对机械分离的大鼠脊髓神经元自发突触后电流的影响。施用士的宁可完全抑制自发突触电流，提示其为甘氨酸能抑制性突触后电流。升高胞外K~(2+)浓度可逆地增加自发性IPSCs的频率，即使在没有胞外K~(2+)的情况下也是如此。河豚毒素对钾诱导的突触增强无影响。在无细胞外Na~(++)存在的情况下，也观察到钾诱导的IPSC频率增加。然而，在无Na~+的条件下，突触增强的恢复明显受到抑制。钾诱导的自发性IPSCs易化可被thapsigargin耗尽细胞内钙离子，提示细胞内钙离子释放有关。这些结果揭示了钾诱导去极化调节突触前神经末梢细胞内钙离子浓度和胞吐的新机制。

The effect of potassium-induced presynaptic depolarization on spontaneous postsynaptic currents under extracellular Ca^<2+>-free conditions was investigated in mechanically dissociated rat spinal cord neurons using whole-cell patch-clamp technique. Spontaneous synaptic currents were fully inhibited by application of strychnine, indicating that they were glycinergic inhibitory postsynaptic currents (IPSCs). Elevating extracellular K^+ concentration reversibly increased that frequency of spontaneous IPSCs even in the absence of extracellular Ca^<2+>. Tetrodotoxin had no effect on the potassium-induced synaptic potentiation. The potassium-induced increase in IPSC frequency was also observed in the absence of extracellular Na^+. However, the recovery from the synaptic potentiation was markedly inhibited in the Na^+-free conditions. The potassium-induced facilitation of spontaneous IPSCs was prevented by depletion of intracellular Ca^<2+> store with thapsigargin, suggesting the contribution of Ca^<2+>-release from intracellular Ca^<2+> stores.These results reveal a novel mechanism by which potassium-induced depolarization regulates the intracellular Ca^<2+> concentration and exocytosis in presynaptic nerve terminals.