Kuruma Akinori, Inoue Takafumi, Mikoshiba Katsuhiko
Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan.
Eur J Neurosci. 2003 Nov;18(10):2677-89. doi: 10.1111/j.1460-9568.2003.02977.x.
Ca2+ and Na+ play important roles in neurons, such as in synaptic plasticity. Their concentrations in neurons change dynamically in response to synaptic inputs, but their kinetics have not been compared directly. Here, we show the mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre stimulation (50 Hz, 3-50-times) depolarized Purkinje cells, and Ca2+ transients were observed at the anatomically expected sites. The magnitude of the Ca2+ transients increased linearly with increasing numbers of parallel fibre inputs. With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached approximately 100 microm, which was much higher than that reported previously, although it was still confined to a part of the dendrite. In contrast, Na+ transients were sustained for tens of seconds and diffused away from the stimulated site. Pharmacological interventions revealed that Na+ influx through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and Ca2+ influx through P-type Ca channels were essential players, that AMPA receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from intracellular stores through inositol trisphosphate receptors or ryanodine receptors did not contribute greatly to the large Ca2+ transients.
钙离子(Ca2+)和钠离子(Na+)在神经元中发挥着重要作用,比如在突触可塑性方面。它们在神经元中的浓度会随着突触输入而动态变化,但其动力学尚未得到直接比较。在此,我们通过同时监测小鼠小脑切片浦肯野细胞树突中的情况,展示了Ca2+和Na+瞬变的机制及动态变化。高频平行纤维刺激(50赫兹,3至50次)使浦肯野细胞去极化,并在解剖学预期部位观察到Ca2+瞬变。Ca2+瞬变的幅度随着平行纤维输入数量的增加而线性增加。施加50次刺激时,Ca2+瞬变持续数秒,[Ca²⁺]峰值达到约100微摩尔,尽管仍局限于树突的一部分,但这一数值比之前报道的要高得多。相比之下,Na+瞬变持续数十秒,并从刺激部位扩散开来。药理学干预表明,通过α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体的Na+内流以及通过P型钙通道的Ca2+内流是关键因素,AMPA受体不作为Ca2+内流途径,并且通过肌醇三磷酸受体或兰尼碱受体从细胞内储存释放Ca2+对大的Ca2+瞬变贡献不大。