Yaari Y, Konnerth A, Heinemann U
J Neurophysiol. 1986 Aug;56(2):424-38. doi: 10.1152/jn.1986.56.2.424.
The role of extracellular K+ (K+o) in nonsynaptic epileptogenesis induced in the CA1 area of rat hippocampal slices by lowering [Ca2]o was studied with K+-selective microelectrodes (KSMs). Extracellular field potentials and [K+]o were recorded simultaneously with 1-2 KSMs in the CA1 stratum pyramidale. In slices perfused with an oxygenated standard physiological solution (containing 2 mM Ca2+), base-line [K+]o was stable for several hours. The washout of Ca2+o was accompanied by a gradual tonic rise of [K+]o. Spontaneous and stimulus-evoked maximal seizurelike events (SLEs) appeared when [K+]o was approximately 0.5 mM above the initial 5 mM base line. These changes were reversible in normal medium. When K+o was pressure ejected in the CA1 stratum pyramidale of spontaneously active slices, a local rise in [K+]o of approximately 0.5 mM was necessary to trigger a SLE. A similar apparent [K+]o "threshold" was associated with SLEs evoked by electrical stimulation. Increasing [K+] in the perfusing solution by small increments (1 mM) markedly enhanced SLEs frequency and velocity of spread and decreased the period of absolute refractoriness that succeeded each paroxysm. Similar changes occurred during periods of transient hypoxia. Small [K+] decreases in the perfusate had the converse effects. Spontaneous SLEs were associated with phasic increases in [K+]o. In simultaneous [K+]o recordings from two layers, these transients were largest (up to 3.5 mM above base line) and rose more steeply at the stratum pyramidale. Toward the outer dendritic layers they became smaller, slower in time course, and delayed in onset. We conclude that the main source for these [K+]o transients are the hippocampal pyramidal cell bodies, which discharge intensely during a SLE, and that excess K+o is spatially dispersed around the discharge zone of the paroxysm. [K+]o continued to rise, though at a slower rate, throughout the course of a SLE. Following SLE termination, [K+]o decayed slowly to base line. The invasion of a CA1 region by a propagating SLE was preceded quite often by a slow rise in [K+]o. A sudden transition to a steeply rising [K+]o marked the explosive recruitment of this region into the discharge zone of the spreading paroxysm. The total (tonic and phasic) increase in [K+]o during SLEs did not surpass a maximal level of approximately 9 mM, which was the ceiling level of [K+]o in low [Ca2+]o. However, when spreading depression occurred, [K+]o rose up to 30-40 mM for several minutes. Spreading depression rarely appeared spontaneously despite the recurrence of SLEs, but could be provoked by repetitive electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
采用钾离子选择性微电极（KSMs）研究了细胞外钾离子（K⁺o）在通过降低细胞外钙离子浓度（[Ca²⁺]o）诱导大鼠海马脑片CA1区非突触性癫痫发生过程中的作用。在CA1锥体层用1 - 2个KSMs同时记录细胞外场电位和K⁺o。在用含氧标准生理溶液（含2 mM Ca²⁺）灌注的脑片中，基线K⁺o在数小时内保持稳定。Ca²⁺o的洗脱伴随着K⁺o的逐渐强直性升高。当K⁺o比初始的5 mM基线高出约0.5 mM时，出现自发和刺激诱发的最大癫痫样事件（SLEs）。在正常培养基中，这些变化是可逆的。当在自发活动的脑片的CA1锥体层通过压力喷射K⁺o时，K⁺o局部升高约0.5 mM才能触发一次SLE。类似的明显K⁺o“阈值”与电刺激诱发的SLEs相关。通过小幅度增加（1 mM）灌注溶液中的K⁺浓度，显著提高了SLEs的频率和传播速度，并缩短了每次发作后绝对不应期的时长。在短暂缺氧期间也出现了类似变化。灌注液中K⁺浓度的小幅降低则产生相反的效果。自发的SLEs与K⁺o的阶段性升高相关。在同时记录两层的K⁺o时，这些瞬变在锥体层最大（比基线高出3.5 mM），且上升更为陡峭。向外周树突层方向，它们变得更小、时间进程更慢且起始延迟。我们得出结论，这些K⁺o瞬变的主要来源是海马锥体细胞体，其在SLE期间强烈放电，并且过量的K⁺o在发作区周围空间扩散。在整个SLE过程中，K⁺o持续升高，尽管速率较慢。SLE终止后，K⁺o缓慢衰减至基线。传播性SLE侵入CA1区之前，K⁺o常常会缓慢上升。K⁺o突然转变为急剧上升标志着该区域突然被纳入扩散性发作的放电区。SLE期间K⁺o的总（强直性和阶段性）升高未超过约9 mM的最大水平，这是低[Ca²⁺]o时K⁺o的上限水平。然而，当发生扩散性抑制时，K⁺o会在几分钟内升至30 - 40 mM。尽管SLEs反复出现，但扩散性抑制很少自发出现，但可由重复性电刺激诱发。（摘要截取自400字）
