Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices
Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices
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DOI：
10.1152/jn.1997.77.1.9
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发表时间：
1997-01-01
影响因子：
2.5
通讯作者：
Somjen, GG
中科院分区：
文献类型：
--
作者：
Largo, C;Tombaugh, GC;Somjen, GG
我们调查了庚醇和其他已知的能阻断缝隙连接的长链醇是否会干扰扩散性抑制(SD)的产生或传播。SD波是通过在地层中微量注入浓氯化钾溶液来触发的(S)。大鼠海马区脑片CA1区的辐射。细胞外电位(V-o)的DC耦合记录在注射时和第二个与st相距1 mm的位置进行。辐射状，有时也在圣彼得堡。金字塔。细胞外兴奋性突触后电位(FEPSP)是通过刺激Schaffer侧支诱发的；在一些实验中，刺激肺泡可以诱发逆行群峰电位。3 mM正庚醇或5 mM正己醇可完全可逆地阻止SD相关电位移位(Delta V-o)的传播，而不会消除注射部位的Delta V-o。辛醇(1 MM)也有类似的可逆作用，但可靠性较低。正庚醇和辛醇对fEPSP的抑制率接近30%，正己醇对fEPSP的抑制率为65%。相反的种群峰值被抑制了30%。在膜片钳分离的CA1区锥体神经元上，庚醇部分地和可逆地抑制电压依赖性钠电流，可能通过作用于突触前动作电位来解释逆行波的轻微抑制和fEPSP的抑制。氟乙酸酯(FAC)是一种可能的胶质代谢选择性阻滞剂，它首先在单个传入放电反应中诱导多个峰放电，然后严重抑制突触传递(证实了先前的报道)，而不抑制反向群体峰电位。FAC对SD的增殖无抑制作用。烷基醇的作用与通常关闭的神经元缝隙连接的开放是SD传播所必需的想法是一致的。另一种可能的解释包括干扰神经细胞膜的脂相。FAC不抑制SD的存在证实了SD的增殖不需要突触传递，这表明正常功能的神经胶质细胞对SD的产生或繁殖不是必不可少的。
We investigated whether heptanol and other long-chain alcohols that are known to block gap junctions interfere with the generation or the propagation of spreading depression (SD). Waves of SD were triggered by micro-injection of concentrated KCl solution in stratum (s.) radiatum of CA1 of rat hippocampal tissue slices. DC-coupled recordings of extracellular potential (V-o) were made at the injection and at a second site similar to 1 mm distant in st. radiatum and sometimes also in st. pyramidale. Extracellular excitatory postsynaptic potentials (fEPSPs) were evoked by stimulation of the Schaffer collateral bundle; in some experiments, antidromic population spikes were evoked by stimulation of the alveus. Bath application of 3 mM heptanol or 5 mM hexanol completely and reversibly prevented the propagation of the SD-related potential shift (Delta V-o) without abolishing the Delta V-o at the injection site. Octanol (1 mM) had a similar but less reliably reversible effect. fEPSPs were depressed by similar to 30% by heptanol and octanol, 65% by hexanol. Antidromic population spikes were depressed by 30%. In isolated, patch-clamped CA1 pyramidal neurons, heptanol partially and reversibly depressed voltage-dependent Na currents possibly explaining the slight depression of antidromic spikes and, by acting on presynaptic action potentials, also the depression of fEPSPs. Fluoroacetate (FAc), a putative selective blocker of glial metabolism, first induced multiple spike firing in response to single afferent volleys and then severely suppressed synaptic transmission (confirming earlier reports) without depressing the antidromic population spike. FAc did not inhibit SD propagation. The effect of alkyl alcohols is compatible with the idea that the opening of normally closed neuronal gap junctions is required for SD propagation. Alternative possible explanations include interference with the lipid phase of neuron membranes. The absence of SD inhibition by FAc confirms that synaptic transmission is not necessary for the propagation of SD, and it suggests that normally functioning glial cells are not essential for SD generation or propagation.