Huang Chin-Wei, Huang Chao-Ching, Wu Sheng-Nan
Department of Neurology, National Cheng-Kung University Medical Center, Tainan, Taiwan.
Epilepsia. 2006 Apr;47(4):720-6. doi: 10.1111/j.1528-1167.2006.00498.x.
Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels can couple an intracellular metabolic state to an electrical activity, which is important in the control of neuronal excitability and seizure propagation. We investigated whether the newer antiepileptic drug, pregabalin (PGB), could exert effects on KATP channels in differentiated hippocampal neuron-derived H19-7 cells.
The inside-out configuration of the patch-clamp technique was used to investigate KATP channel activities in H19-7 cells in the presence of PGB. Effects of various compounds known to alter KATP channel activities were compared.
The activity of KATP channels in these cells was characterized. The single-channel conductance from a linear current-voltage relation was 78 +/- 2 pS (n = 8) with a reversal potential of 63 +/- 2 mV (n = 8), similar to that of KATP channels reported in pancreatic beta cells. 2,4-Dinitrophenol activated channel activity, but the further addition of glucose (20 mM) or glibenclamide (30 microM) could offset these increments. PGB significantly opened these KATP channel activities in a concentration-dependent fashion with a median effective concentration (EC50) value of 18 microM. A significant increase was noted in the mean open lifetime of KATP channels in the presence of PGB (1.71 +/- 0.04 to 5.62 +/- 0.04 ms).
This study suggests that in differentiated hippocampal neuron-derived H19-7 cells, the opening effect on KATP channels could be one of the underlying mechanisms of PGB in the reduction of neuronal excitability.
三磷酸腺苷（ATP）敏感性钾离子（KATP）通道可将细胞内代谢状态与电活动相耦联，这对控制神经元兴奋性和癫痫传播很重要。我们研究了新型抗癫痫药物普瑞巴林（PGB）是否能对分化的海马神经元来源的H19-7细胞中的KATP通道产生影响。
采用膜片钳技术的内面向外模式，在有PGB存在的情况下研究H19-7细胞中的KATP通道活性。比较了已知可改变KATP通道活性的各种化合物的作用。
对这些细胞中KATP通道的活性进行了表征。根据线性电流-电压关系得出的单通道电导为78±2 pS（n = 8），反转电位为63±2 mV（n = 8），与胰腺β细胞中报道的KATP通道相似。2,4-二硝基苯酚激活通道活性，但进一步添加葡萄糖（20 mM）或格列本脲（30 μM）可抵消这些增加。PGB以浓度依赖性方式显著开放这些KATP通道活性，半数有效浓度（EC50）值为18 μM。在有PGB存在的情况下，KATP通道的平均开放寿命显著增加（从1.71±0.04至5.62±0.04毫秒）。
本研究表明，在分化的海马神经元来源的H19-7细胞中，对KATP通道的开放作用可能是PGB降低神经元兴奋性的潜在机制之一。
