N'gouemo Prosper, Faingold Carl L, Morad Martin
Department of Pediatrics, Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington, DC 20057, United States.
Neuropharmacology. 2009 Mar;56(3):665-75. doi: 10.1016/j.neuropharm.2008.11.005. Epub 2008 Dec 6.
Voltage-gated calcium (Ca(2+)) channels are thought to play an important role in epileptogenesis and seizure generation. Here, using the whole cell configuration of patch-clamp techniques, we report on the modifications of biophysical and pharmacological properties of high threshold voltage-activated Ca(2+) channel currents in inferior colliculus (IC) neurons of the genetically epilepsy-prone rats (GEPR-3s). Ca(2+) channel currents were measured by depolarizing pulses from a holding potential of - 80 mV using barium (Ba(2+)) as the charge carrier. We found that the current density of high threshold voltage-activated Ca(2+) channels was significantly larger in IC neurons of seizure-naive GEPR-3s compared to control Sprague-Dawley rats, and that seizure episodes further enhanced the current density in the GEPR-3s. The increased current density was reflected by both a - 20 mV shifts in channel activation and a 25% increase in the non-inactivating fraction of channels in seizure-naive GEPR-3s. Such changes were reduced by seizure episodes in the GEPR-3s. Pharmacological analysis of the current density suggests that upregulation of L-, N- and R-type of Ca(2+) channels may contribute to IC neuronal hyperexcitability that leads to seizure susceptibility in the GEPR-3s.
电压门控钙（Ca(2+)）通道被认为在癫痫发生和发作产生中起重要作用。在此，我们采用膜片钳技术的全细胞模式，报告了遗传性癫痫易感大鼠（GEPR - 3s）下丘（IC）神经元中高阈值电压激活的Ca(2+)通道电流的生物物理和药理学特性的改变。以钡（Ba(2+)）作为电荷载体，通过从 - 80 mV的钳制电位进行去极化脉冲来测量Ca(2+)通道电流。我们发现，与对照的斯普拉格 - 道利大鼠相比，未发作的GEPR - 3s的IC神经元中高阈值电压激活的Ca(2+)通道的电流密度显著更大，并且癫痫发作进一步增强了GEPR - 3s中的电流密度。电流密度的增加表现为通道激活向负20 mV偏移以及未发作的GEPR - 3s中通道非失活部分增加25%。在GEPR - 3s中，癫痫发作使这些变化减小。对电流密度的药理学分析表明，L型、N型和R型Ca(2+)通道的上调可能导致GEPR - 3s中IC神经元的过度兴奋，从而导致癫痫易感性。
