Franceschetti Silvana, Lavazza Tatiana, Curia Giulia, Aracri Patrizia, Panzica Ferruccio, Sancini Giulio, Avanzini Giuliano, Magistretti Jacopo
National Neurological Institute "C. Besta", 20133 Milan; and Department of Physiological and Pharmacological Sciences, University of Pavia, 27100 Pavia, Italy.
J Neurophysiol. 2003 Apr;89(4):2101-11. doi: 10.1152/jn.00695.2002.
The ionic mechanisms underlying the termination of action-potential (AP) bursts and postburst afterhyperpolarization (AHP) in intrinsically bursting (IB) neocortical neurons were investigated by performing intracellular recordings in thin slices of rat sensorimotor cortex. The blockade of Ca(2+)-activated K(+) currents enhanced postburst depolarizing afterpotentials, but had inconsistent and minor effects on the amplitude and duration of AHPs. On the contrary, experimental conditions resulting in reduction of voltage-dependent Na(+) entry into the cells caused a significant decrease of AHP amplitude. Slice perfusion with a modified artificial cerebrospinal fluid in which LiCl (40 mM) partially replaced NaCl had negligible effects on the properties of individual APs, whereas it consistently increased burst length and led to an approximately 30% reduction in the amplitude of AHPs following individual bursts or short trains of stimulus-induced APs. Experiments performed by partially replacing Na(+) ions with choline revealed a comparable reduction in AHP amplitude associated with an inhibition of bursting activity. Moreover, in voltage-clamp experiments carried out in both in situ and acutely isolated neurons, partial substitution of extracellular NaCl with LiCl significantly and reversibly reduced the amplitude of K(+) currents evoked by depolarizing stimuli above-threshold for Na(+)-current activation. The above effect of Na(+)-to-Li(+) substitution was not seen when voltage-gated Na(+) currents were blocked with TTX, indicating the presence of a specific K(+)-current component activated by voltage-dependent Na(+) (but not Li(+)) influx. The above findings suggest that a Na(+)-activated K(+) current recruited by the Na(+) entry secondary to burst discharge significantly contributes to AHP generation and the maintenance of rhythmic burst recurrence during sustained depolarizations in neocortical IB neurons.
通过在大鼠感觉运动皮层薄片上进行细胞内记录，研究了内在爆发性（IB）新皮层神经元中动作电位（AP）爆发终止和爆发后超极化（AHP）的离子机制。Ca(2+)激活的K(+)电流的阻断增强了爆发后的去极化后电位，但对AHP的幅度和持续时间有不一致且较小的影响。相反，导致电压依赖性Na(+)进入细胞减少的实验条件会使AHP幅度显著降低。用LiCl（40 mM）部分替代NaCl的改良人工脑脊液灌注薄片，对单个AP的特性影响可忽略不计，而它持续增加爆发长度，并导致单个爆发或短串刺激诱发的AP后的AHP幅度降低约30%。用胆碱部分替代Na(+)离子进行的实验显示，AHP幅度有类似降低，同时爆发活动受到抑制。此外，在原位和急性分离神经元中进行的电压钳实验中，用LiCl部分替代细胞外NaCl显著且可逆地降低了高于Na(+)电流激活阈值的去极化刺激诱发的K(+)电流幅度。当用TTX阻断电压门控Na(+)电流时，未观察到上述Na(+)到Li(+)替代的效应，表明存在由电压依赖性Na(+)（而非Li(+)）内流激活的特定K(+)电流成分。上述发现表明，由爆发放电继发的Na(+)进入募集的Na(+)激活K(+)电流对新皮层IB神经元持续去极化期间AHP的产生和节律性爆发复发的维持有显著贡献。
