Schmitt H, Meves H
Physiologisches Institut der Universitat des Saarlandes, Homburg-Saar, Germany.
J Physiol Paris. 1995;89(4-6):181-93. doi: 10.1016/0928-4257(96)83635-7.
Three types of ionic current essentially determine the firing pattern of nerve cells: the persistent Na+ current, the M current and the low-voltage-activated Ca(2)+ current. The present article summarizes recent experiments concerned with the basic properties of these currents. Keynes and Meves (Proc R Soc Lond B (1993) 253, 61-68) studied the persistent or steady-state Na+ current on dialysed squid axons and measured the probability of channel opening both for the peak and the steady-state Na+ current (PF(peak) and PF(ss)) as a function of voltage. Whereas PF(peak) starts to rise at -50 mV and reaches a maximum at +40 to +50 mV, PF(ss) only begins to rise appreciably at around 0 mV and is still increasing at +100 mV. This differs from observations on vertebrate excitable tissues where the persistent Na+ current tums on in the threshold region and saturates at around 0 mV. Schmitt and Meves (Pflugers Arch (1993) 425, 134-139) recorded M current, a non-inactivating K+ current, from NGI08-15 neuroblastoma x glioma hybrid cells, voltage-clamped in the whole-cell mode, and studied the effects of phorbol 12,13-dibutyrate (PDB), an activator of protein kinase C (PKC), and arachidonic acid (AA). PDB and AA both decreased I(M), the effective concentrations being 0.1-1 mu M and 5-25 mu M, respectively; while the PDB effect was regularly observed, the M current depression by AA was highly variable from cell to cell. The PKC 19-31 peptide, an effective inhibitor of PKC, in a concentration of 1 muM almost totally prevented the effects of PDB and AA on M current, suggesting that both are mediated by PKC. Schmitt and Meves (Pflugers Arch (1994a) 426, Suppl R 59) measured low-voltage-activated (l-v-a) and high-voltage-activated (h-v-a) Ca2+ currents on NG108-15 cells and investigated the effect of AA and PDB on both types of current. At pulse potentials > -20 mV, AA (25-100 mu M) decreased 1-v-a and h-v-a I(Ca). The decrease was accompanied by a small negative shift and a slight flattening of the activation and inactivation curves of the l-v-a I(Ca). The AA effect was not prevented by 50 mu M eicosa-5,8,11,14-tetraynoic acid (ETYA), an inhibitor of AA metabolism, or PKC 19-31 peptide and not mimicked by 0.1-1 mu M PDB. Probably, AA acts directly on the channel protein or its lipid environment. The physiological relevance of these three sets of observations is briefly discussed.
持续钠电流、M电流和低电压激活的钙电流。本文总结了近期有关这些电流基本特性的实验。凯恩斯和梅韦斯（《伦敦皇家学会学报B》（1993年）253卷，61 - 68页）研究了透析乌贼轴突上的持续或稳态钠电流，并测量了峰值和稳态钠电流通道开放概率（PF(peak)和PF(ss)）随电压的变化。PF(peak)在 - 50 mV时开始上升，在 + 40至 + 50 mV时达到最大值，而PF(ss)仅在约0 mV时才开始明显上升，在 + 100 mV时仍在增加。这与在脊椎动物可兴奋组织中的观察结果不同，在脊椎动物中持续钠电流在阈值区域开启并在约0 mV时达到饱和。施密特和梅韦斯（《普弗吕格尔斯文献》（1993年）425卷，134 - 139页）在全细胞模式下电压钳制的NGI08 - 15神经母细胞瘤×胶质瘤杂交细胞中记录了M电流，一种非失活钾电流，并研究了佛波醇12,13 - 二丁酸（PDB），一种蛋白激酶C（PKC）激活剂，和花生四烯酸（AA）的作用。PDB和AA都降低了I(M)，有效浓度分别为0.1 - 1 μM和5 - 25 μM；虽然PDB的作用经常被观察到，但AA对M电流的抑制在细胞间差异很大。PKC 19 - 31肽，一种有效的PKC抑制剂，浓度为1 μM时几乎完全阻止了PDB和AA对M电流的影响，表明两者均由PKC介导。施密特和梅韦斯（《普弗吕格尔斯文献》（1994a年）426卷，增刊R 59）测量了NG108 - 15细胞上的低电压激活（l - v - a）和高电压激活（h - v - a）钙电流，并研究了AA和PDB对这两种电流的影响。在脉冲电位 > - 20 mV时，AA（25 - 100 μM）降低了l - v - a和h - v - a I(Ca)。这种降低伴随着l - v - a I(Ca)激活和失活曲线的小负移和轻微变平。50 μM二十碳 - 5,8,11,14 - 四炔酸（ETYA），一种AA代谢抑制剂，或PKC 19 - 31肽不能阻止AA的作用，且0.1 - 1 μM PDB也不能模拟其作用。可能，AA直接作用于通道蛋白或其脂质环境。简要讨论了这三组观察结果的生理相关性。
